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Objective: The current study aimed to investigate whether Cocos nucifera L. oil (CO) is effective on menopause-related memory dysfunction in ovariectomized (OVX) rats. Materials and Methods: Fifty healthy female Wistar rats were randomly selected and classified into five groups as control, OVX rats, and three OVX groups of rats which received three different doses (100, 200, and 400 mg/kg/day) of CO for five consecutive weeks by gavage. To assess the effect of CO, neurobehavioral tests such as Morris water maze (MWM) and Passive avoidance (PA) were done and then the animals were sacrificed to remove cortical and hippocampal tissues for biochemical analysis. Results: In both behavioral tests including MWM and PA, treatment with CO particularly two higher doses of 200, and 400 mg/kg demonstrated significant improvement in comparison with OVX group. Furthermore, antioxidant biomarkers such as total thiol content, catalase and superoxide dismutase (SOD) activities were significantly higher in the OVX-CO groups versus the OVX group. On the contrary, malondialdehyde (MDA) concentration as an oxidative stress biomarker was remarkably lower in the OVX-CO200 and 400 mg groups than the OVX group. Conclusion: The present study demonstrated the significant improvement of CO on learning and memory impairment induced by ovariectomy. Although the exact mechanism needs further investigation, it might have occurred due to the anti-oxidative effect of CO. [ABSTRACT FROM AUTHOR]

Incensole acetate (IA) is a major component of Boswellia serrata resin that has been shown to have anti-inflammatory, anti-oxidant and neuroprotective properties. The present study determined the effect of IA on lipopolysaccharide (LPS)-induced memory impairment, and hippocampal cytokines and oxidative stress indicators level. We used 32 Wistar rats (220–250 g weight) randomly divided into four groups. The control group, which only received the saline-diluted DMSO (vehicle); LPS group which received LPS and was treated with the vehicle; and two IA-treated groups which received 2.5 or 5 mg/ kg IA before LPS injection. Morris water maze (MWM) and passive avoidance (PA) tests were performed. Finally, the brains were removed and were used to assess cytokines levels and oxidative stress status. Compared to the LPS group, IA administration reduced the time spent and path traveled to reach the hidden platform during 5 days of learning in MWM while increased the time spent in the target quadrant in the probe test. Moreover, IA increased latency while decreased entry number and time spent in the dark chamber of PA test compared to the LPS group. Additionally, pre-treatment with IA attenuated interleukin(IL)-6, tumor necrosis alpha (TNF-α), glial fibrillary acidic protein (GFAP), malondialdehyde (MDA) and nitric oxide (NO) metabolites levels while increased those of IL-10, total thiol, superoxide dismutase (SOD), catalase (CAT) and brain-derived neurotrophic factor (BDNF). Our results indicated that IA improved LPS-induced learning and memory impairments. The observed effects seem to be mediated via a protective activity against neuro-inflammation and brain tissue oxidative damage and through improving BDNF. [ABSTRACT FROM AUTHOR]

Nigella sativa (N. sativa) was shown to recover fatigue and imbalanced immune system. Therefore, effect of chronic administration of N. sativa hydroethanolic extract on splenocytes response in sedentary and exercised animals, was evaluated. Male Wistar rats were randomly divided into non-treated (control sedentary (C), moderately trained (MT; Velocity 20 m/min, 30 min/day 8 weeks), and over-trained (OT; Velocity 25 m/min, 60 min/day 11 weeks)), and N. sativa-treated animals (Nisa, 200 mg/kg, orally) (control (Nisa-C), moderately trained (Nisa-MT) and over-trained (Nisa-OT)). Finally, cell viability and proliferation, as well as interleukin 4 (IL-4) and interferon-γ (IFN-γ) secretion in non-stimulated and concanavalin A (Con A)-stimulated splenocytes, were evaluated. In the absence of the mitogen, cell viability in Nisa-C and Nisa-OT, cell proliferation in Nisa-C and Nisa-MT, IFN-γ concentration in Nisa-MT and Nisa-OT and IFN-γ/IL-4 ratio in Nisa C, Nisa-MT and Nisa-OT were higher compared to non-treated groups; but, IL-4 level in Nisa-MT was lower than non-treated groups. In the presence of the mitogen, cell viability in Nisa-C and Nisa-OT, IL-4 concentration in Nisa-C and Nisa-OT groups, and IFN-γ concentration and IFN-γ/IL-4 ratio in Nisa-MT were higher, while IFN-γ/IL-4 ratio was lower in Nisa-C group compared to non-treated groups. Moreover, IFN-γ/IL-4 ratio in stimulated and non-stimulated splenocytes supernatant was higher in Nisa-MT compared to Nisa-C and Nisa-OT groups. N. sativa chronic administration may shift Th1/Th2 cytokines profile of splenocytes towards Th1, especially in over-trained and non-stimulated condition. Moderate exercise and N. sativa supplementation may improve disorders associated with elevated Th2 such as overtraining syndrome. [ABSTRACT FROM AUTHOR]

The effect of moderate and overtraining exercise on Th1/Th2 balance was evaluated in rat splenocytes. Male Wistar rats were divided into sedentary control (C), moderately trained (MT; V = 20 m/min, 30 min/day, 8 weeks), overtrained (OT; V = 25 m/min, 60 min/day, 11 weeks) and recovered after overtraining (OR) (OT plus 2 weeks recovery) groups. At the end of study, cell viability, proliferation, interleukin 4 (IL-4) and interferon-g (IFN-g) secretion were evaluated in non-stimulated, phytohemagglutinin (PHA) and concavaline A (Con A)-stimulated splenocytes. Cell viability increased in MT and OR groups compared to control. Cell proliferation was higher in OR group than other groups. IL-4 concentration in PHA-stimulated cells from MT and OT groups, and IL-4 concentration in Con A-stimulated cells from OR and OT groups, were higher than the control group, but not for IFN-g. In non-stimulated cells, IFN-g/IL-4 ratiowas higher than MTand OTgroups. In PHA and Con A-stimulated cells, IFN-g/IL-4 ratiowas lower in exercise groups than control. We previously showed that moderate exercise increases Th1 cytokines in serum, but in splenocytes, Th2 or Th1 response may increase depending on the type of mitogen stimulation. Two-week recovery restored Th1/Th2 balance, only in non-stimulated splenocytes of overtrained animals. [ABSTRACT FROM AUTHOR]

Tramadol, a frequently used pain reliever drug, present neurotoxic effects associated to cognitive dysfunction. Moreover, crocin has been reported to have neuroprotective effects. The aim of this study was to assess crocin’s capacity to protect learning, and memory abilities on tramadol-treated rats. A total of 35 rats were divided into five groups: Control, Saline, tramadol (50 mg/kg), tramadol + crocin(30 mg/kg), crocin groups and treated orally for 28 consecutive days. Morris water maze (MWM) and passive avoidance (PA) tests were done, followed by dissection of the rat’s brains for toluidine blue and TUNEL staining. In MWM test, tramadol group spent lower time and traveled shorter distance in the target quadrant (Q1) (P < 0.05). On the other side, the traveled distance in tramadol-crocin group was higher than tramadol (P < 0.05). In PA test, both the delay for entering the dark, and the total time spent in the light compartment decreased in tramadol comparing to the control group (P < 0.05), while it increased in tramadol-crocin compared with the tramadol group (P < 0.05). In tramadol-treated animals, the dark neurons (DNs) and apoptotic cells in CA1, CA3 and DG increased (P < 0.05), while concurrent intake of crocin decreased the number of DNs and apoptotic cells in these areas (P < 0.05). Crocin was able to improve learning and memory of tramadol-treated rats and also decreased DNs and apoptotic cells in the hippocampus. Considering these results, the potential capacity of crocin for decreasing side effects of tramadol on the nervous system is suggested. [ABSTRACT FROM AUTHOR]

The effects of vitamin E (Vit E) on brain derived neurotrophic factor (BDNF) and brain tissues oxidative damage as well as on learning and memory impairments in juvenile hypothyroid rats were examined. The rats were grouped as: (1) Control; (2) Propylthiouracil (PTU); (3) PTU-Vit E and (4) Vit E. PTU was added to their drinking water (0.05%) during 6 weeks. Vit E (20 mg/kg) was daily injected (IP). Morris water maze (MWM) and passive avoidance (PA) were carried out. The animals were deeply anesthetized and the brain tissues were removed for biochemical measurements. PTU increased the escape latency and traveled path in MWM (P < 0.001). It also shortened the latency to enter the dark compartment of PA as well as the time spent in the target quadrant in probe trial of MWM (P < 0.01-P < 0.001). All the effects of PTU were reversed by Vit E (P < 0.01-P < 0.001). PTU administration attenuated thiol and BDNF content as well as the activities of superoxide dismutase (SOD) and catalase (CAT) in the brain tissues while increased molondialdehyde (MDA). Moreover, Vit E improved BDNF, thiol, SOD and CAT while diminished MDA. The results of the present study showed that Vit E improved BDNF and prevented from brain tissues oxidative damage as well as learning and memory impairments in juvenile hypothyroid rats. [ABSTRACT FROM AUTHOR]

Objective(s): Cholinergic neurons are important neurons in the Pedunculopontine tegmental nucleus (PPT). In this study, nicotinic receptor of the PPT in central cardiovascular regulation in the anesthetized rat was evaluated. Materials and Methods: Saline, acetylcholine (Ach; doses: 90 and 150 nmol), hexamethonium (Hexa; doses: 100 and 300 nmol) and higher doses of Hexa (300 nmol) + Ach (150 nmol) microinjected into the PPT. The femoral artery was cannulated and cardiovascular responses were continuously recorded by a power lab system. After injection of drugs, peak changes of mean arterial pressure (AMAP), systolic blood pressure (ASBP) and heart rate (AHR) calculated and compared with saline group. Results: The ASBP and AMAP significantly decreased by two doses of Ach (P<0.05 to P<0.001) but AHR did not change. Two doses 100 (P<0.05) and 300 nmol (P<0.01) of Hexa significantly increased AHR but did not alter the AMAP or ASBP. Co-injection of Hexa + Ach significantly strengthened the AHR induced by Hexa alone (P<0.01) but did not affect AMAP or ASBP. Conclusion: These results indicate that nicotinic receptor of the PPT has an inhibitory effect on AHR with no significant effect on AMAP or ASBP. [ABSTRACT FROM AUTHOR]

BACKGROUND: Subclinical inflammation induced by persistent exposure to lipopolysaccharide (LPS) is found in some clinical conditions such as obesity or diabetes. This study aimed to investigate the effect of recurrent LPS exposure on inflammatory markers, oxidative stress balance and cardiac and renal fibrosis in male rats. METHODS: Male Wistar rats were divided into control and LPS-treated. LPS (10 mg/kg/week) was injected intraperitoneally. After 4 weeks, left ventricles and kidneys were homogenized and stained with hematoxylin and eosin (H&E) and Masson trichrome for histological examination. Serum levels of nitrite, interleukin 6 (IL-6) and tumor necrosis factor-a (TNF-a) were measured and total thiol, malondialdehyde (MDA), superoxide dismutase (SOD) and catalase were evaluated in the heart and kidney homogenates. RESULTS: Serum inflammatory markers were higher in LPS group than control (nitrite: 37.0 ± 2.2 vs. 25.5 ± 1.9 µmol/l; IL-6: 84 ± 3 vs. 98.0 ± 4.4 pg/ml; TNF-a: 75.5 ± 4.9 vs. 85.3 ± 4.7 pg/ml; respectively, P < 0.050). Evaluation of total thiol concentration (heart: 10.0 ± 0.9 vs. 22.5 ± 1.2; kidney: 7.0 ± 0.5 vs. 27.8 ± 3.1 nmol/g tissue, respectively), catalase (heart: 0.18 ± 0.03 vs. 0.66 ± 0.04; kidney: 0.17 ± 0.03 vs. 0.73 ± 0.03, U/g tissue, respectively) and SOD (heart: 8.01 ± 0.70 vs. 12.3 ± 0.4; kidney: 7.02 ± 0.60 vs. 12.0 ± 0.2, U/g tissue, respectively) showed lower levels in LPS-treated group compared to control; while MDA concentration in LPS group was higher than control (P < 0.05). Histopathological examination in LPS-treated group indicated infiltration of inflammatory cells and more collagen deposition in left ventricle wall and kidney compared to control group. CONCLUSION: We concluded that in clinical conditions with chronic LPS, cardiac and renal fibrosis occurs even in absence of preceding tissue injury due to imbalances in oxidative stress. [ABSTRACT FROM AUTHOR]

The effects of tamoxifen and soy on apoptosis of the hippocampus and dentate gyrus of ovariectomized rats after repeated seizures were investigated. Female rats were divided into: (1) Control, (2) Sham, (3) Sham-Tamoxifen (Sham-T), (4) Ovariectomized (OVX), (5) OVX-Tamoxifen (OVX-T), (6)OVX-Soy(OVX-S) and (7) OVX-S-T. The animals in the OVX-S, OVX-T and OVX-S-T groups received soy extract (60 mg/kg; i.p.), tamoxifen (10 mg/kg) or both for 2 weeks before induction of seizures. The animals in these groups additionally received the mentioned treatments before each injection of pentylenetetrazole (PTZ; 40 mg/kg) for 6 days. The animals in the Sham and OVX groups received a vehicle of tamoxifen and soy. A significant decrease in the seizure score and TUNEL-positive neurons was seen in the OVX group compared to the Sham (P < 0.001). The animals in both the OVX-T and OVX-S groups had a significantly higher seizure score as well as number of TUNEL-positive neurons compared to the OVX group (P < 0.01–P < 0.001). Co-treatment of the OVX rats by the extract and tamoxifen decreased the seizure score and number of TUNEL-positive neurons compared to OVX-S (P < 0.001). Treatment of the OVX rats by either soy or tamoxifen increased the seizure score as well as the number of TUNEL-positive neurons in the hippocampal formation. Co-administration of tamoxifen and soy extract inhibited the effects of the soy extract and tamoxifen when they were administered alone. It might be suggested that both soy and tamoxifen have agonistic effects on estrogen receptors by changing the seizure severity. [ABSTRACT FROM AUTHOR]

Everolimus (EVR), as a rapamycin analog, is a selective inhibitor of the mammalian target of rapamycin (mTOR) kinase and its associated signaling pathway. mTOR is a serine/threonine protein kinase and its hyperactivity is involved in the pathophysiology of Alzheimer's disease (AD) and associated cognitive deficits. The present study evaluated the impact of EVR, on cognitive functions, hippocampal cell loss, and neurochemical parameters in the intracerebroventricular streptozotocin (icv-STZ) model of AD rats. EVR (1 and 5 mg/kg) was administered for 21 days following the single administration of STZ (3 mg/kg, icv) or for 7 days on days 21-28 post-STZ injection after establishment of cognitive dysfunction. Cognitive deficits (passive avoidance and spatial memory), oxidative stress parameters, acetylcholinesterase (AChE) activity, and percentage of cell loss were evaluated in the hippocampus. Chronic administration (1 and 5 mg/kg for 21 days from the day of surgery and icv-STZ infusion) or acute injection (5 mg/kg for 7 days after establishment of cognitive impairment) of EVR significantly attenuated cognitive dysfunction, neuronal loss, oxidative stress and AChE activity in the hippocampus of STZ-AD rats. In conclusion, our study showed that EVR could prevent or improve deteriorations in behavioral, biochemical and histopathological features of the icv-STZ rat model of AD. Therefore, inhibition of the hyperactivated mTOR may be an important therapeutic target for AD. [ABSTRACT FROM AUTHOR]

Objective(s): Nitric oxide (NO) is an important neurotransmitter in central nervous system involved in central cardiovascular regulation. The presence of NO in the pedunculopontine tegmental (PPT) nucleus has been shown, but its cardiovascular effect has not been determined. In the present study, the cardiovascular effect of NO in the PPT nucleus was evaluated. Materials and Methods: After induction of anesthesia, a polyethylene catheter (PE-50) filled with heparinized saline inserted into the femoral artery, and the blood pressure (BP) and heart rate (HR) were continuously recorded. Animals were then placed in a stereotaxic apparatus and maximum changes of mean arterial pressure (ΔMAP) and heart rate (ΔHR) after microinjection of two doses of NG-nitro-L-arginine methyl ester (L-NAME, 30 and 90 nmol), L-arginine (L-Arg 10 and 50 nmol) and sodium nitroprusside (SNP, 9 and 27 nmol) into the PPT were provided and compared with control group (One-way ANOVA). Results: Both doses of L-NAME significantly increased ΔMAP compared to control (P<0.05 and P<0.01, respectively). ΔHR only in higher dose (90 nmol) significantly increased compared to control (P<0.05). Two doses of L-Arg (10 and 50 nmol/150 nl) had no significant effect on ΔMAP or ΔHR. Higher dose of SNP (27 nmol) significantly decreased ΔMAP (P<0.05) and its both doses significantly decreased ΔHR compared to control (P<0.05 and P<0.001, respectively). Effect of higher dose on ΔHR was significantly higher than the lower dose (P<0.05). Conclusion: Our results show an inhibitory effect of the nitrergic system of the PPT on central cardiovascular system. [ABSTRACT FROM AUTHOR]

In this study the effects of Vitamin C (Vit C) on hypothyroidism-associated learning and memory impairment in juvenile rats was investigated. The pregnant rats were kept in separate cages. After delivery, they were randomly divided into six groups and treated: (1) Control; (2) Propylthiouracil (PTU) which 0.005% PTU in their drinking; (3-5) Propylthiouracil- Vit C groups; besides PTU, dams in these groups received 10, 100 and 500 mg/kg Vit C respectively, (6) one group as a positive control; the intact rats received an effective dose, 100 mg/kg Vit. C. After delivery, the pups were continued to receive the experimental treatments in their drinking water up to 56th day of their life. Ten male offspring of each group were randomly selected and tested in the Morris water maze (MWM) and passive avoidance (PA) which were started at 63th day (one week after stopping of the treatments). Brains were then removed for biochemical measurements. PTU increased time latency and traveled distance during 5 days in MWM while, reduced the spent time in target quadrant in MWM and step-trough latency (STL) in PA. PTU decreased thiol content, superoxide dismutase (SOD) and catalase (CAT) activities in the brain while, increased molondialdehyde (MDA). In MWM test, 10, 100 and 500 mg/kg Vit C reduced time latency and traveled distance without affecting the traveling speed during 5 days. All doses of Vit C increased the spent time in target quadrant in probe trail of MWM and also increased STL in PA test. Vit C increased thiol, SOD and CAT in the brain tissues while, reduced MDA. Results of present study confirmed the beneficial effects of Vit C on learning and memory. It also demonstrated that Vit C has protective effects on hypothyroidism-associated learning and memory impairment in juvenile rats which might be elucidated by the antioxidative effects. [ABSTRACT FROM AUTHOR]

Objective: The neuroprotective effects of both garlic and ascorbic acid (AA) have been documented. In this study the effects of garlic and ascorbic acid on memory deficits and brain tissue oxidative damages induced by lead exposure was investigated.Methods: The juvenile rats were divided and treated: (1) Control, (2) Lead (lead acetate in drinking water, 8 weeks), (3) Lead – Ascorbic Acid (Lead-AA), (4)  Lead – Garlic (100 mg/kg, daily, gavage) (Lead-Gar).Results: In Morris water maze (MWM), the escape latency and traveled path in the Lead group were significantly higher while, the time spent in the target quadrant (Q1) was lower than Control. Both Lead-Gar and Lead-AA groups spent more times in Q1than to lead group. There were no significant differences in swimming speed between the groups. In passive avoidance (PA) test, the time latency for entering the dark compartment by Lead group was lower than Control. Treatment of the animals by AA and garlic significantly increased the time latency. In Lead group, the total thiol concentration in brain tissues was significantly lower while, MDA was higher than Control. Treatment by both garlic and AA increased total thiol concentrations and decreased MDA. Both garlic and AA decreased the lead content of brain tissues.Conclusion: It is suggested that treatment with garlic attenuates the learning and memory impairments due to lead exposure during juvenile rat growth which is comparable to AA. The possible mechanism may be due to its protective effects against brain tissues oxidative damage as well the lowering effects of brain lead content. [ABSTRACT FROM PUBLISHER]

Objective: Coriandrum sativum (C. sativum) as a medicinal plant has been pointed to have analgesic, hypnotic and anti-oxidant effects. In the current study, a possible preventive effect of the hydro-alcoholic extract of the plant on neuronal damages was examined in pentylenetetrazole (PTZ) rat model of seizure. Materials and Methods: Forty male rats were divided into five main groups and treated by (1) saline, (2) PTZ: 100 mg/kg PTZ (i.p) and (3-5) 50, 100 and 200 mg/kg of hydro-alcoholic extract of C. sativum during seven consecutive days before PTZ injection. After electrocorticography (ECoG), the brains were removed to use for histological examination. Results: All doses of the extract reduced duration, frequency and amplitude of the burst discharges while prolonged the latency of the seizure attacks (p<0.05, p<0.01, and p<0.001). Administration of all 3 doses of the extract significantly prevented from production of dark neurons (p<0.01, and p<0.001) and apoptotic cells (p<0.05, p<0.01, and p<0.001) in different areas of the hippocampus compared to PTZ group. Conclusion: The results of this study allow us to conclude that C. sativum, because of its antioxidant properties, prevents from neuronal damages in PTZ rat model of seizure. [ABSTRACT FROM AUTHOR]

Objectives: It has been shown that hypothyroidism-induced oxidative damage in brain tissue is involved in its adverse effects on learning and memory.Nigella sativa(N. sativa) has been suggested to have antioxidant and neuroprotective effects. The objective of this study was to investigate the effects of hydroalcoholic extract ofN. sativaon hypothyroidism-associated learning and memory impairment during neonatal and juvenile growth in rats. Methods: Thirty pregnant rats were kept in separate cages. After delivery, the mothers and their offspring were randomly divided into six groups including: (1) control, (2) PTU (propylthiouracil), (3) PTU-NS 100, (4) PTU-NS 200, (5) PTU-NS 400, and (6) PTU-Vit C (vitamin C). All dams except the control group received 0.005% PTU in their drinking water during lactation. Besides PTU, dams in groups 3, 4, 5, and 6 received 100, 200, and 400 mg/kgN. sativaextract, or 100 mg/kg Vit C, respectively. After lactation period, pups continued to receive same experimental treatment for the first 8 weeks of their life. Then, 10 male offspring of each group were randomly selected and assessed for the learning and memory abilities by using Morris water maze (MWM) and passive avoidance (PA) tests. Blood samples were collected for thyroxine assessment, animals were euthanized, and the brain tissues were removed and analyzed for total thiol groups and malondialdehyde (MDA) concentrations. Results: PTU exposure significantly increased the time latency in MWM test, while reduced the time spent in target quadrant, and decreased the latency for entering the dark compartment in PA test. These effects were associated with significant reduction in serum thyroxine levels and brain levels of thiol groups, and significant elevation in hippocampal MDA. Administration of 400 mg/kgN. sativaextract and 100 mg/kg Vit C reduced the time latency, while increased the time spent in target quadrant compared to the PTU group in MWM test. Treatment by 100–400 mg/kg ofN. sativaextract and also Vit C significantly increased the time latency for entering the dark compartment in PA test. The serum thyroxine concentrations of the animals treated by all doses of theN. sativaextract as well as by Vit C were higher than that of the PTU group. Two hundred and four hundred milligrams/kilogram of NS extract and 100 mg/kg Vit C decreased the MDA concentration in hippocampal tissues, while increased thiol contents compared to the PTU group. Discussion: The results of this study demonstrate that the hydroalcoholic extract ofN. sativahave protective effects on hypothyroidism-associated learning and memory impairment during neonatal and juvenile growth in rats. The effects were comparable to Vit C and might be due to the protective effects ofN. sativaextract against brain tissues’ oxidative damage. [ABSTRACT FROM PUBLISHER]

Nanoscale titanium dioxide (TiO2), which is massively produced and widely used in living environment, seems to have a potential risk on human health. The central nervous system (CNS) is the potential susceptible target of nanoparticles, but the studies on this aspect are limited so far. The aim of this study was to evaluate the effects of exposure to TiO2 nanoparticles during lactation period on learning and memory of offspring. Lactating Wistar rats were exposed to TiO2 nanoparticles (100 mg/kg; gavage) for 21 days. The Morris water maze and passive avoidance tests showed that the exposure to TiO2 nanoparticles could significantly impair the memory and learning in the offspring. Therefore, the application of TiO2 nanoparticles and the effects of their exposure, especially during developmental period on human brain should be cautious. [ABSTRACT FROM AUTHOR]

Background/aim: The effects of coadministration of melatonin and theanine (Mel/Thea) on pentylenetetrazole (PTZ)-induced seizures and brain tissue oxidative damage were investigated in ovariectomized (OVX) and sham-operated rats. Materials and methods: The rats were divided into the following groups: 1) sham, 2) ovariectomized (OVX), 3) sham-PTZ, 4) OVXPTZ, 5) sham-Mel/Thea-PTZ, and 6) OVX-Mel/Thea-PTZ. Groups 1-4 received saline, while groups 5 and 6 received a combination of Mel/Thea for 6 weeks. All animals except for those in groups 1 and 2 received a single injection of PTZ. Results: The OVX-PTZ group had higher generalized tonic-clonic seizure (GTCS) latency compared to the sham-PTZ group. Administration of Mel/Thea increased minimal clonic seizure and GTCS latencies in both the sham-Mel/Thea-PTZ and OVX-Mel/Thea- PTZ groups compared to the controls. Additionally, PTZ exposure increased malondialdehyde levels and reduced thiol concentrations in brain tissues of both the sham-PTZ and OVX-PTZ groups. Mel/Thea pretreatment resulted in MDA reduction and thiol increase in brain tissues. Conclusion: The results of this study demonstrated the antioxidant and anticonvulsant activities of Mel/Thea despite the presence or absence of ovarian hormones. [ABSTRACT FROM AUTHOR]

Background Regarding the similar modulatory effects of both soy and tamoxifen on the actions of estrogen which have previously reported, the aim of the present study was to investigate the effects of these two estrogen like compounds alone and in combination on dark neuron production in hippocampal formation of ovariectomized rats after pentylenetetrazole-induced repeated seizure. Methods The rats were randomly divided into six groups: control, sham, OVX, OVX-soy (OVX-S), OVX-tamoxifen (OVX-T) and OVX-soy-tamoxifen (OVX-S-T). The animals of OVX-S, OVX-T and OVX-S-T groups received the soy extract (60 mg/kg; i.p.), tamoxifen (10 mg/kg) or both for 2 weeks before induction of seizures. The animals of these groups were also treated by soy extract, tamoxifen or both before each injection of PTZ (40 mg/kg) for 6 days. The animals of sham and OVX groups received saline plus tween instead of tamoxifen and soy extract. The animals of control group did not treat by PTZ, tamoxifen and soy. The rats were placed in Plexiglas cages separately and observed for 60 min. The brain tissues were then removed and subjected for histological studies. Results A significant decrease in the seizure score was seen in OVX group comparing to sham. The animals of both OVX-T and OVX-S groups had a significant higher seizure score compared to OVX group. Co-treatment of the ovariectomized rats by both soy extract and tamoxifen decreased the seizure score compared to OVX-S and OVX-T groups. The results of histological study showed that the dark neuron number in CA1, CA2, CA3 and dentate gyrus (DG) of hippocampus area in OVX-T and OVX-S groups was higher than that of OVX group ( P < 0.05– P < 0.01). In CA3, the produced dark neurons of OVX-S-T group were lower than that OVX-S group ( P < 0.01). Conclusion The results of present study showed that treatment of the ovariectomized rats by either soy extract or tamoxifen increased the seizure score as well as dark neurons. Co-treatment with soy extract and tamoxifen did not potentiate the effects of each of them alone. Co-administration of the tamoxifen and soy extract inhibited the effects of the soy extract and tamoxifen when they administered alone. [ABSTRACT FROM AUTHOR]

Regarding the therapeutic properties of Nigella sativa (NS), the effects of the plant hydro - alcoholic extract on learning, memory and brain tissues oxidative damage were investigated in penthylenetetrazole (PTZ) - induced repeated seizures. There were 4 experimental groups including: 1- control group; received saline, 2- PTZ group ; received saline and PTZ (50 mg/Kg, i.p) , 3-PTZ- NS 200 and 4- PTZ- NS 400 ; received 200 and 400 mg/Kg of NS extract respectively, before PTZ injection in 5 consecutive days. Seizure scores were lower in PTZ - NS 200 and 400, furthermore the seizure onset latencies were higher in these groups than PTZ group (P<0.05 and P<0.01 ). In Morris water maze, the time spent in target quadrant by PTZ group was lower than control group (P<0.05); while, 400 mg/Kg of the extract increased it (P<0.01). In the passive avoidance test, delay time to enter the dark by PTZ group was lower than control at 1 and 24 hours after training (P<0.01- P<0.001); while, 400 mg/Kg of the extract increased it (P<0.05). The total thiol concentration in hippocampal and cortical tissues of PTZ group was reduced while, MDA concentration was higher than control (p<0.05 - p<0.001). Administration of the extract increased the total thiol and decreased the MDA concentrations (p<0.01- p<0.001). It is concluded that the hydro-alcoholic extract of NS possess beneficial effects on learning and memory impairments in repeated seizures model which is accompanied by antioxidant effects in the brain. [ABSTRACT FROM AUTHOR]

Background: Neuroimmune factors have been considered as contributors to the pathogenesis of depression. Beside other therapeutic effects, Valeriana officinalis L., have been suggested to have anti-inflammatory effects. In the present study, the effects of V. officinalis L. hydro alcoholic extract was investigated on depression like behavior in ovalbumin sensitized rats. Materials and Methods: A total of 50 Wistar rats were divided into five groups: Group 1 (control group) received saline instead of Valeriana officinalis L. extract. The animals in group 2 (sensitized) were treated by saline instead of the extract and were sensitized using the ovalbumin. Groups 3-5 (Sent - Ext 50), (Sent - Ext 100) and (Sent - Ext 200) were treated by 50, 100 and 200 mg/kg of V. officinalis L. hydro-alcoholic extract respectively, during the sensitization protocol. Forced swimming test was performed for all groups and immobility time was recorded. Finally, the animals were placed in the open-field apparatus and the crossing number on peripheral and central areas was observed. Results: The immobility time in the sensitized group was higher than that in the control group (P < 0.01). The animals in Sent-Ext 100 and Sent-Ext 200 groups had lower immobility times in comparison with sensitized group (P < 0.05 and P < 0.01). In the open field test, the crossed number in peripheral by the sensitized group was higher than that of the control one (P < 0.01) while, the animals of Sent-Ext 50, Sent-Ext 100 and Sent-Ext 200 groups had lower crossing number in peripheral compared with the sensitized group (P < 0.05 and P < 0.01 respectively). Furthermore, in the sensitized group, the central crossing number was lower than that of the control group (P < 0.001). In the animals treated by 200 mg/kg of the extract, the central crossing number was higher than that of the sensitized group (P < 0. 05). Conclusions: The results of the present study showed that the hydro-alcoholic extract of V. officinalis prevents depression like behavior in ovalbumin sensitized rats. These results support the traditional belief on the about beneficial effects of V. officinalis in the nervous system. Moreover, further investigations are required in order to better understand this protective effect. [ABSTRACT FROM AUTHOR]

Objective(s): The effect of prolonged overtraining on cytokine kinetics was compared with moderate exercise in the present study. Materials and Methods: Male Wistar rats were randomly divided into control sedentary (C), moderate trained (MT), (V=20 m/min, 30 min/day for 6 days a week, 8 weeks), overtrained (OT) (V=25 m/min, 60min/day for 6 days a week, 11 weeks) and recovered overtrained (OR) (OT plus 2 weeks recovery) groups, (n=6 for each group). Immediately, 24 hr and 2 weeks (in OR) after last bout of exercise blood samples were obtained. The plasma concentrations of TNFα, IL-6, IL-10, IL-4 and IFNγwere measured by ELISA method. Results: Immediately after last bout of exercise the following findings were observed; IL-6, IL-10 and TNFα concentrations increased in OT and OR groups compared with control (P<0.05-P<0.001). Serum level of IL-4 decreased (P<0.01) but IFNγ increased (P<0.05) in MT group vs. control. In addition, circulatory levels of TNFα, IL-6, IL-10 and IL-4 were higher but the IFNγconcentrations were lower in OT and OR groups than MT group (P<0.05-P<0.01). The IFN-γ/IL4 ratio was significantly increased in MT (P<0.01) while it decreased in OT group. There were not statistical differences in TNFα, IL-6, and IFNγlevels between different time intervals after exercise in MT, OT and OR groups. Conclusion: These data confirm a positive effect of moderate exercise on immune function and a decrease in susceptibility to viral infection by inducing Th1 cytokine profile shift. However, prolonged and overtraining exercise causes numerous changes in immunity that possibly reflects physiological stress and immune suppression. [ABSTRACT FROM AUTHOR]

Abstract: Introduction and objective: Beneficial effects of glucosamine in spatial learning and memory impairment induced by scopolamine has been evaluated in rats by using Morris water maze. Methods: Male Wistar rats were randomly divided into control, scopolamine and scopolamine plus glucosamine groups. All injections were given in 5 consecutive days and 30min after each injection, the rats were tested in the Morris water maze test. Escape latency and path length to reach the hidden platform were subjected to analysis of variance [ANOVA]. Results: The rats treated with scopolamine showed increased escape latency and path length to reach the hidden platform compared to control group (P <0.001). Both escape latency and traveled path length to reach the hidden platform in glucosamine treated animals (1 and 2g/kg) were significantly lower (P <0.05 to P <0.001) than in the scopolamine group. Conclusion: The results of this study showed that the glucosamine can inhibit scopolamine-induced impairments of spatial learning and memory in rats. Glucosamine might offer a promise in either the prevention or the treatment of neurodegenerative diseases such as Alzheimer's disease. [Copyright &y& Elsevier]

Summary: Human umbilical cord blood (HUCB) is now considered as a valuable source for stem cell-based therapies. Previous studies showed that intravascular injection of the HUCB significantly improves neurological functional recovery in a model of intracerebral hemorrhage (ICH). To extend these findings, we examined the behavioral recovery and injured volume in the presence of increasing doses of human umbilical cord blood derived mononuclear cells (HUC-MCs) after intracerebral hemorrhage in rats. The experimental ICH was induced by intrastriatal administration of bacterial collagenase IV in adult rats. One day after the surgery, the rats were randomly divided into 4 groups to receive intravenously either BrdU positive human UC-MCs (4×106, 8×106 and 16×106 cells in 1ml saline, n =10, respectively) as treated groups or the same amount of saline as lesion group (n =10). There was also one group (control n =10) that received only the vehicle solution of collagenase. The animals were evaluated for 14 days with modified limb placing and corner turn tests. The transplanted human UC-MCs were also detected by immunohistochemistry with labeling of BrdU. Two weeks after infusion, there was a significant recovery in the behavioral performance when 4×106 or more UC-MCs were delivered (P <0.05–0.001). Injured volume measurements disclosed an inverse relationship between UC-MCs dose and damage reaching significance at the higher UC-MCs doses. Moreover, human UC-MCs were localized by immunohistochemistry only in the injured area. Intravenously transplanted UC-MCs can accelerate the neurological function recovery of ICH rat and diminish the striatum lesion size by demonstrating a dose relationship between them. [Copyright &y& Elsevier]

Introduction: The role of ovarian hormones and nitric oxide (NO) on oxidative damage in brain tissues as well as learning and memory has been widely investigated. The present study was carried out to evaluate the effect of the precursor of NO, L-Arginine on learning and brain damage due to oxidative stress in ovariectomized (OVX) rats. Methods: Thirty -two rats were divided into four groups: 1) Sham, 2) OVX, 3) Sham-L- Arginine (Sham-LA) and 4) OVX-L-Arginine(OVX-LA). The animals of sham- LA and OVX-LA were treated with 500 mg/kg of L-Arginine. The animals in Sham and OVX groups received 1 ml/kg saline. The animals were tested in Morris water maze and finally, the brains were removed and MDA and total thiol concentrations were measured. Results: The escape latency and swimming path in OVX group were significantly higher than in Sham group (p<0.01). The animals in OVX-LA group had significantly lower swimming path length and escape latency compared to OVX group (p<0.01) while, there was no significant difference between Sham- LA and Sham groups. In OVX-LA group, the brain tissues total thiol concentration was significantly higher, and MDA concentration was lower than of OVX group (p<0.001). There was no significant difference between Sham-LA and Sham groups. Discussion: It seems that the beneficial properties of L-Arginine on spatial learning of ovariectomized rats are in part due to its protective capacity against oxidative damage. [ABSTRACT FROM AUTHOR]

Background: Neuroimmune factors have been proposed as contributors to the pathogenesis of depression. Beside other therapeutic effects including neuroprotective, antioxidant, anticonvulsant and analgesic effects, Nigella sativa and its main ingredient, thymoquinone (TQ), have been shown to have anti-inflammatory effects. In the present study, the effects of Nigella sativa hydro-alcoholic extract and thymoquinone was investigated on lipopolysaccharide- induced depression like behavior in rats. Materials and Methods: 50 male Wistar rats were divided into 5 groups: Group 1 (control group) received saline instead of NS extract, thymoquinone or lipopolysaccharide. The animals in group 2 (lipopolysaccharide (LPS)) were treated by saline instead of NS extract and were injected LPS (100 μg/kg, ip) 2 hours before conducting each forced swimming test. Groups 3 (LPS + NS 200) and 4 (LPS + NS 400) were treated by 200 and 400 mg/kg of NS (ip), respectively, from the day before starting the experiments and before each forced swimming test. These animals were also injected LPS 2 hours before conducting each swimming test. The animals in group 5 received TQ instead of NS extract. Forced swimming test was performed 3 times for all groups (in alternative days), and immobility time was recorded. Finally, the animals were placed in an open- field apparatus, and the crossing number on peripheral and central areas was observed. Results: The immobility time in the LPS group was higher than that in the control group in all 3 times (P < 0.001). The animals in LPS + NS 200, LPS + NS 400 and LPS + TQ had lower immobility times in comparison with LPS groups (P < 0.01, and P < 0.01). In the open- field test, the crossing number of peripheral in the LPS group was higher than that of the control one (P < 0.01) while the animals of LPS + NS 200, LPS + NS 400 and LPS + TQ groups had lower crossing number of peripheral compared with the LPS group (P < 0.05, and P < 0.001). Furthermore, in the LPS group, the central crossing number was lower than that of the control group (P < 0.01). In the animals treated by NS or TQ, the central crossing number was higher than that of the LPS group (P < 0.05, and P < 0.001). Conclusions: The results of the present study showed that hydro-alcoholic extract of Nigella sativa can prevent LPS-induced depression like behavior in rats. These results support the traditional belief on the beneficial effects of Nigella sativa in the nervous system. Moreover, further investigations are required in order to better understand this protective effect. [ABSTRACT FROM AUTHOR]

Abstract: The cuneiform nucleus (CnF) is a sympathoexcitatory area involved in the central cardiovascular regulation. Its role in the maintaining vasomotor tone has, however, not yet been clarified. In the present study the effects of cobalt chloride (CoCl2) a nonselective synapse blocker and NMDA and non-NMDA glutamate receptors on resting mean arterial blood pressure and heart rate of CnF have been evaluated. CoCl2, AP5 (an NMDA receptor antagonist) and CNQX (an AMPA/kinase receptor antagonist) (100nl) were microinjected into the CnF of anesthetized rats. The blood pressure and heart rate were recorded throughout the experiment. The responses of blood pressure and heart rate were compared with the pre-injection (paired t-test) and control (independent t-test) values. Microinjection of CoCl2, AP5 and CNQX did not change the basal blood pressure and heart rate. In conclusion, our present study indicates that the CnF is not important in the regulation of cardiovascular tone. [Copyright &y& Elsevier]

Objective(s) Human umbilical cord blood (HUCB) is now considered as a valuable source for stem cell-based therapies. Previous studies showed that intravascular injection of the HUCB significantly improves neurological functional recovery in a rat model of intracerebral hemorrhage (ICH). In the present study, we hypothesize transplanted HUCB derived mononuclear cells (UC-MCs) can decrease injured volume and also ameliorate neurological function in ICH rats. Materials and Methods Experimental ICH was induced by intrastriatal administration of collagenase in rats. One day after surgery, the rats were divided into 3 groups to receive intravenously either BrdU positive human UC-MCs [(4x106 and 8x106 cells in 1 ml saline, n=10 respectively) as treated groups] or the same amount of saline [as lesion group (n=10)]. There was also one group (control) that received only vehicle solution of collagenase. The animals were evaluated for 14 days with behavioral tests. Transplanted UC-MCs were detected by immunohistochemistry. Histological data and scores of functional tests were analyzed using ANOVA. Cellular co-localization of BrdU+ cells in the histological slides was determined by software Image J. Results Intravenously transplanted UC-MCs migrated selectively to the hematomal area and reduce injured volume. The UC-MCs transplanted groups showed better performance on functional tests after 2 weeks compared with the lesion and control groups (P< 0.05). There was no difference in the functional recovery and injured volume improvement between the 2 treated groups. Conclusion Intravenously transplanted UC-MCs accelerate neurological function recovery of ICH rat and diminish the striatum lesion size. Thus these cells may provide a potential cell candidate for cell-based therapy in ICH. [ABSTRACT FROM AUTHOR]

Objective: The role of ovarian hormones and nitric oxide on morphine-induced antinociception and their interaction have been widely investigated. The results of previous study showed that nitric oxide synthase inhibition differently affects morphine-induced antinociception in male and female rats. The present study was carried out to evaluate the different effects of chronic administration of L-arginine (LA) and L-NAME (LN) on morphine-induced antinociception in ovariectomized (OVX) and naive female rats. Materials and Methods: Sixty female rats were randomly divided into six groups (n = 10) as follows: (1) sham, (2) OVX, (3) sham-LA (4) sham-LN (5) OVX-LA, and (6) OVX-LN. The animals of sham-LA and OVX-LA groups received daily injection of 200 mg/kg LA (i.p.) during 6 weeks, while in sham-LN and OVX-LN groups, the animals were treated with 10 mg/kg LN (i.p.). The animals of sham and OVX groups received 2 ml/kg saline (i.p.) instead of LA and LN. Finally, all the animals were tested on the hot plate test (52 ± 0.2°C; cut-off time 80 seconds) for evaluating the antinociceptive effects of morphine. The hot plate test was performed as three base records with a 15-min interval before the injection of morphine (10 mg/kg; s.c.) following which it was repeated every 15 min after injection. Analgesic effect of morphine was quantified as maximal percent effect (MPE). Base reaction latency times (seconds) before the injection of morphine and MPE after the injection of morphine were compared using repeated-measure analysis of variance (ANOVA) followed by post-hoc Tukey's test. Differences were considered statistically significant when P < 0.05. Results: Before injection of morphine, there was no significant difference observed between sham and OVX groups in three recorded base reaction latency times. The base reaction latency times in sham-LA group were significantly higher than those of sham group (P < 0.001). In sham-LN group, the base reaction latency times were nonsignificantly lower than those of sham group (P = 0.095). There was no significant difference between OVX-LA group and OVX group. In OVX-LN group, three base reaction latency times were nonsignificantly lower than those of OVX group (P = 0.077). MPE in sham-LN group was higher than that of sham group (P < 0.05); however, there was no significant difference between sham-LA and sham groups. Conclusion: It is concluded that NO has a role in pain perception and the analgesic effect of morphine. The effect of NO might be differing in the presence or absence of ovarian hormones, but further investigations need to be done. [ABSTRACT FROM AUTHOR]

Abstract: The roles of gonadal hormones and nitric oxide on pain perception and their interaction have been widely investigated. In the present study the chronic effect of l-NAME (NOS inhibitor) on morphine-induced antinociception in male and female rats was investigated. Forty rats were divided into four groups: (1) female (2) female-LN (3) male (4) and male-LN. The animals of groups 2 and 4 received daily injection of l-NAME (10mg/kg) during 3 weeks. The animals of control groups 1 and 3 received 2ml/kg saline instead of l-NAME. Finally, all animals were tested on the hot plate test (52±0.2°C; Cut-off 80s) to evaluate the antinociceptive effects of morphine. The hot plate test was performed for base record 15min before the injection of morphine (10mg/kg; s.c.) and consequently it was repeated every 15min after the injection. There were no significant differences in baseline latencies among all groups. Reaction times after injection of morphine in female-LN were higher than in the female control group (p <0.01). There was, however, no significant difference between male control and male-LN groups. Reaction times in the female-LN group were significantly higher than in the male-LN group. Reaction times after injection of morphine in the male group was longer than in the female group (p <0.01). It is concluded that sex hormones such as testosterone and estrogen have a role in pain perception and analgesia. NO has a modulatory effects on functions of sex hormones in pain perception and analgesic effects of opioids. [Copyright &y& Elsevier]

Background: Locus coeruleus is one of important involved sites in morphine withdrawal signs, contains high densities of Angiotensin II receptor binding sites. In this study the effect of microinjection of Angiotensin II and captopril to the Locus coeruleus on morphine withdrawal signs was evaluated. Methods: Male wistar rats were anesthetized and stainless style cannula implanted in the locus coeruleus and allowed to recover from surgery. Morphine was injected 3 times in each day for 4 days to induce morphine dependence. The animals divided into 3 groups; control group received saline and case groups received Angiotensin II (1 nanomole) or captopril (30 μg) before naloxone injection. After naloxone injection, morphine withdrawal signs were assessed and compared between groups. Findings: In Angiotensin group, some of withdrawal signs such as wet dog shakes was significantly higher than saline group (P < 0.05). Expression of some of withdrawal signs such as jumping in Angiotensin group was decreased more than saline group (P < 0.01). Also, in captopril group some of withdrawal signs such as wet dog shakes was significantly higher than those of saline group (P < 0.05. Expression of some of withdrawal signs such as writhing posture, teeth chattering, grooming, genital grooming and head shakes were decreased in captopril group more than saline group (P < 0.05). Conclusion: We suggest that Angiotensin II have some roles in opioid withdrawal through locus coeruleus nucleous which contains considerable receptors for it. [ABSTRACT FROM AUTHOR]

Abstract: Exercise can activate the same pathways as morphine. The aim of the present study was to clarify the effect of short-term and mid-term exercises on the self-administration of morphine in rats. Male Wistar rats were initially trained to receive small pellets of food by pressing the active lever in self-administration apparatus. Rats were divided into 4 groups: Saline, Morphine, Exercise 1 (11 days) and Exercise 2 (30 days). Their jugular vein was cannulated. The animals were placed in self-administration apparatus and allowed to self-administer morphine (0.5mg per infusion all test groups) or saline (Saline group) during consecutive days, for 2h/sessions. In the group 1 the rats were running before each session of self-administration and of group Exercise 2, 30 days before surgery as well as before each session. The pressing numbers of active and passive levers in each group and among different groups were compared. The number of active lever pressing of Morphine group was significantly higher than Saline group (p <0.001). In Exercise 1 and Exercise 2 groups, the number of active lever pressing was significantly lower than Morphine group (p <0.001). As exercise can activate many neurotransmitter systems involved in the addiction process and increase the release of endorphins, it is likely that could decrease the morphine self-administration in this experimental setup. [Copyright &y& Elsevier]

Abstract: The rennin–angiotensin system (RAS) has been implicated in the development of diabetic vascular complications. Peptidyl-dipeptidase A (angiotensin converting enzyme, ACE) has a major role in this system. The aim of the present study was to clarify the effect of intraperitoneal administration of aqueous garlic extract (Allium sativum) on the serum ACE activity of streptozotocin (STZ)-diabetic and nondiabetic rats. Although garlic extract administration had no significant effect on serum glucose, it significantly strongly decreased the serum ACE activity. ACE activity was higher in diabetic than nondiabetic rats, but in diabetic animals treated with garlic extract, the elevation of ACE activity did not occur. These results suggest that garlic extract might have value as ACE inhibitor to prevent some vascular complications of diabetes mellitus. [Copyright &y& Elsevier]

Background: 5-Bromo-2-deoxyuridine (BrdU) has been a principal marker for mitotic cells in studies of adult neurogenesis. The method consists of a pulse injection of BrdU into the intraperitoneal cavity followed by a variable survival time allowing for tracking the divided cells and their progeny. However, such exogenous markers may produce toxic effects. Aim of this study was determined the effects of Brdu on spatial memory in the adult rat. Materials and Methods: 16 Wistar rats were used in this experimental study. The rats were randomly divided into 2 groups (N=8 in each group), as follows: control and Brdu (50 mg/kg). Brdu was administered intraperitoneally for 6 weeks and then animals were used for behavioral testing in the Morris water maze. The data were analyzed with repeated measure's ANOVA. Results: Our present findings show that there were no differences in the path length, escape latency and swim speed between control and Brdu-administrated groups. Conclusion: This study show that Brdu (exogenic proliferation marker) did not has side effects on spatial memory in the adult rats. [ABSTRACT FROM AUTHOR]

The current study was designed to investigate the protective effects of Vitamin D (VD) on hippocampal neurogenesis, apoptosis, and subsequent hippocampal-dependent learning and memory performance in hypothyroid juvenile rats. Twenty eight male Wistar rats were randomly divided into four groups as; control, Hypothyroid (Hypo), Hypo-VD100 and Hypo-VD500. Hypothyroidism was induced by giving 0.05 % propylthiouracil (PTU), and VD (100 or 500 IU/kg) treatment was performed daily by gavage. At the end of treatment, Morris water maze (MWM) was carried out and evaluated hippocampal neurogenesis, apoptosis, and dark neurons (DNs). Our results revealed that the escape latency and the traveled distance to find the platform in the Hypo group were significantly longer but the time spent and distance traveled in the target area in probe trial was lower than the control group. Hypothyroidism was accompanied by a marked decrease in hippocampal neurogenesis, and a significant increase in the number of apoptotic neurons and DNs compared to the control group. VD decreased escape latency and the traveled distance to find the platform but increased the time spent and distance traveled in the target area in probe trial than the Hypo group. VD also increased neurogenesis, reduced apoptosis and DNs production compared to the Hypo group. In conclusion, these results support a role for VD in the restoring hippocampal neurogenesis impairment, reducing neuronal apoptosis, and DNs in hypothyroid rats as well as raise the possibility that VD may contribute as a therapeutic approach to improve the learning and memory deficits associated with hypothyroidism. [ABSTRACT FROM AUTHOR]

Diazinon (DZN) an organophosphate (OP), with the most important mechanism of action of DZN being induction of oxidative stress (OS) and inhibition of the enzyme acetylcholinesterase (AChE). Verbascum cheiranthifolium (VER) and Biebersteinia multifida (BM) belong to the Scrophulariaceae and Biebersteiniaceae family respectively. These plants are widely used in Iranian traditional medicine due to their beneficial effects. Thus, this research aimed to appraise the protective effects of the methanolic extract of the VER and BM on changes in the level of expression of α7 and α4 subunits of nicotinic acetylcholine receptors (nAChRs) in hippocampus (HPC) of DZN-treated rats. In this research, 36 male Wistar rats were used and randomly divided into six groups: Control, DZN (40 mg/kg), VER (1 g/kg), DZN+VER (40 mg/kg+1 g/kg), BM (150 mg/kg), and DZN+BM (40 mg/kg+150 mg/kg). At the end of treatment periods, the animals of all groups underwent the Morris water maze (MWM) test. The rats were anesthetized, and blood sampling was performed. Eventually, the brain was removed for histological study and evaluation of OS parameters. The results indicated that DZN increased the extent of expression of nAChRs in the HPC and significantly inhibited cholinesterase (ChEs) activity plus OS parameters. Also, in MWM, the time to find the platform was significantly longer in the DZN group, while the time and the distance in the probe test were lower than in the control groups. VER and BM extract in the treatment groups simultaneously improved the extent of expression of nAChRs, ChEs activity, as well as the parameters of OS and spatial memory significantly. In conclusion, our results support the neuroprotective properties of VER and BM extract versus DZN in rats. Accordingly, the extracts of VER and BM may be useful as an approach for the treatment of learning disorders and memory enhancement. [Display omitted] • Induction of oxidative stress and Inhibition of AChE level following DZN toxicity. • DZN changed distribution and expression of nAChRs in the hippocampus. • BM and VER extracts can reduce DZN -induced learning and memory disorders in rats. • The methanolic extract of BM and VER improved nAChR expression in the hippocampus. [ABSTRACT FROM AUTHOR]

Objective The study objective was to determine the protective effects of thymoquinone (TQ) on brain tissues oxidative stress status, hippocampal cytokine level, and learning and memory deficits induced by lipopolysaccharide (LPS) in rats. Methods Animals were randomly divided into the following groups and treated: (1) Control (saline), (2) LPS (1 mg/kg i.p.), (3–5) 2, 5 or 10 mg/kg TQ extract 30 min before LPS injection. The treatment was started since two weeks before the behavioral experiments and continued during the behavioral tests (LPS injected 2 h before each behavioral experiment). Finally, the brains were removed for biochemical assessments. Results Morris water maze (MWM) test results showed that LPS increased escape latency compared to control group whereas TQ decreased them vs. LPS group. In passive avoidance (PA) test, LPS reduced the latency to enter the dark compartment vs. control group, while TQ treatment attenuated this effect of LPS. Additionally, LPS increased interleukin-6 (IL-6) and tumor necrosis alpha (TNF-α) in the hippocampal tissues. It also elevated malondialdehyde (MDA) and nitric oxide (NO) metabolites and decreased thiol content, superoxide dismutase (SOD) and catalase (CAT) in both hippocampus and cortex vs. control group, while TQ decreased IL-6, TNF-α, MDA and NO metabolites and increased thiol content, SOD and CAT compared to LPS group. Conclusion Findings of current study indicated that TQ improved LPS-induced learning and memory impairments induced by LPS in rats by attenuating the hippocampal cytokine levels and brain tissues oxidative damage. [ABSTRACT FROM AUTHOR]

Highlights: [•] Maternal exposure to titanium dioxide nanoparticles declines cell proliferation in the offspring hippocampus. [•] Maternal exposure to titanium dioxide nanoparticles significantly impairs memory in the offspring. [•] Maternal exposure to titanium dioxide nanoparticles significantly impairs spatial memory in the offspring. [ABSTRACT FROM AUTHOR]

Highlights: [•] Microinjection of Ach in CnF induced hypotension with no effect on HR. [•] Blockade of muscarinic receptors by atropine in CnF strongly attenuate hypotension induced by Ach. [•] Blockade of nicotinic receptors by hexametunium in CnF slightly attenuate hypotension induced by Ach. [•] Effect of CnF muscarinic receptor in cardiovascular regulation is higher than nicotinic receptor. [Copyright &y& Elsevier]

The neuroimmune system has been suggested to play a role in the ethiology of depression and anxiety. Frankincense extract is an herb that has been considered to be an anti-inflammatory agent potentially useful in the treatment of specific neuroimmune system disorders. The present study examined the effects of frankincense ethyl acetate extract on lipopolysaccharide (LPS) - induced depression and anxiety-like behavior in rats. Fifty male Wistar rats received vehicle, 1 mg/kg LPS or 50, 100 or 200 mg/ kg of extract with LPS for 6 days. Forced swim test (FST), elevated plus-maze (EPM) and open field (OF) tests were done in order to assess depression and anxiety-like behaviors. Serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α) levels were evaluated to measure the anti-inflammatory properties of the extract. LPS resulted in depression and anxiety-like behaviors (increased immobility in the FST, decreased time in the central area in the OF, and reduced time in the open arms in the EPM, as well as increased markers of inflammation (IL-6 and TNF-α). Behaviors consistent with anxiety and depression, as well as increased markers of inflammation were reduced by frankincense extract treatment, especially at the highest, 200 mg/kg dose. We conclude that the ethyl acetate extract of frankincense extract can mitigate the LPS-induced depression and anxiety-like behaviors in behavioral testing through reduction of inflammatory cytokines. [ABSTRACT FROM AUTHOR]