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The purpose of this study was to examine whether baicalin (BAI) improves spatial cognitive impairments induced in rats following the repeated administration of the exogenous stress hormone corticosterone (CORT). The effect of BAI on the hippocampal expression of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) was also investigated. For 21 days, male rats received daily doses of BAI (20, 50, and 100 mg/kg, i.p.) 1 h prior to a CORT (40 mg/kg) injection. The daily administration of BAI improved memory impairment as measured by the passive avoidance test and reduced the escape latency for finding the platform in the Morris water maze test. Additionally, as assessed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis, the administration of BAI also significantly alleviated memory-associated decreases in the expression levels of BDNF and CREB proteins and mRNAs in the hippocampus. These results demonstrate that the administration of BAI prior to high-dose exogenous CORT results in significant neuroprotective activity against neuronal impairment and memory dysfunction in rats. Thus, these findings suggest that BAI might be useful as a therapeutic agent in various neurodegenerative diseases for the improvement of cognitive function. This likely occurs through the regulation of BDNF and CREB expression.

Objective: Phosphatidylserine, a major acidic phospholipid in the brain, has been studied extensively in regard to its actions on brain functions. The present study examined the effects of Krill phosphatidylserine (Krill-PS) on the learning and memory function and the neural activity in the normal young rats., Methods: The rats were administered saline or Krill-PS (Krill-PS 50, 100 mg/kg, per oral) daily for 30 days. The cognitive improvement effect of Krill-PS on the normal young rats was investigated by assessing the Morris water maze (MWM) test and by insulin-like growth factor (IGF) and brain-derived neurotrophic factor (BDNF) immunohistochemistry. A positron emission tomography (PET) scan was also performed., Results: Treatment with Krill-PS (100 mg/kg) produced a significant improvement of the escape latency to find the platform in the MWM at the 3rd day compared to that of the normal group. In the retention test, the Krill-PS100 group showed markedly increased time spent, distance, and crossing number around the platform compared to that of the normal group. Consistent with the behavioral data, the Krill-PS 100 group was significantly enhanced the BDNF and IGF immuno-positive neurons in the hippocampal CA1. In the PET analysis, the glucose uptake of the Krill-PS-treated groups was increased in the frontal lobe and hippocampus. These results suggest that repeated Krill-PS treatment may be useful for improving the cognitive function via regulation of neuronal growth factor activity.

Many studies have shown that the steamed root of Rehmannia glutinosa (SRG), which is widely used in the treatment of various neurodegenerative diseases in the context of Korean traditional medicine, is effective for improving cognitive and memory impairments. The purpose of this study was to examine whether SRG extracts improved memory defects caused by administering scopolamine (SCO) into the brains of rats. The effects of SRG on the acetylcholinergic system and proinflammatory cytokines in the hippocampus were also investigated. Male rats were administered daily doses of SRG (50, 100, and 200 mg/kg, i.p.) for 14 days, 1 h before scopolamine injection (2 mg/kg, i.p.). After inducing cognitive impairment via scopolamine administration, we conducted a passive avoidance test (PAT) and the Morris water maze (MWM) test as behavioral assessments. Changes in cholinergic system reactivity were also examined by measuring the immunoreactive neurons of choline acetyltransferase (ChAT) and the reactivity of acetylcholinesterase (AchE) in the hippocampus. Daily administration of SRG improved memory impairment according to the PAT, and reduced the escape latency for finding the platform in the MWM. The administration of SRG consistently significantly alleviated memory-associated decreases in cholinergic immunoreactivity and decreased interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) mRNA expression in the hippocampus. The results demonstrated that SRG had a significant neuroprotective effect against the neuronal impairment and memory dysfunction caused by scopolamine in rats. These results suggest that SRG may be useful for improving cognitive functioning by stimulating cholinergic enzyme activities and alleviating inflammatory responses.

The ameliorating effect of phosphatidylserine (PS) isolated from krill (KR-PS) on the learning and memory deficits associated with normal aging in rats was investigated, as compared with soybean PS (SOY-PS). Rats were orally administered with KR-PS (20, 50 mg kg-1) and SOY-PS (50 mg kg-1) daily, for 7 days, 30 min before behavioral assessment using the Morris water maze (MWM). Changes in the cholinergic system were examined by measuring choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) immunoreactivity in the hippocampus. The daily administration of KR-PS produced a significant improvement in the escape latency for finding the platform in the MWM, as compared with SOY-PS. Consistent with the behavioral results, KR-PS treatments significantly alleviated age-associated losses of cholinergic immunoreactivity, and muscarinic acetylcholine receptor type 1 (mAChR-M1) and choline transporter (CHT) mRNA expression in the hippocampus. These findings demonstrate that KR-PS showed significant neuroprotective activity against the neuronal and cognitive impairments that occur with normal aging in rats; comparable results were obtained with SOY-PS. These data indicate that oral administration of PS derived from marine life could substitute for bovine cerebral cortex PS (BC-PS) as therapy for the improvement of diminished memory function in elderly people.

We investigated the neuritogenic effects of Tremella fuciformis (TF), which has been valued in traditional Chinese medicine as a remedy with nutritive and tonic actions, on PC12h cells. The cognitive improving effects of TF on scopolamine-induced (2 mg/kg, s.c.) amnesia in rats were also evaluated with using the Morris water maze task and by performing choline acetyltransferase (ChAT) immunohistochemistry. The water extract of TF (0.01-1 microg/ml) promoted neurite outgrowth of the PC12h cells in a dose dependent manner. TF was highly efficient at the concentration range of 0.1-1 microg/ml. Oral daily treatment with TF (100 or 400 mg/kg) for 14 consecutive days significantly reversed the scopolamine-induced deficit in learning and memory, and it alleviated decrease in cholinergic immunoreactivity induced by scopolamine in the medial septum and hippocampus. The results demonstrate that the promotion of neuritogenesis in neuronal culture cells by TF water extract is related with its activity for improving the performance of rats on a spatial learning and memory task. Moreover, the impairments of spatial learning and memory may be attributable to the decrease in activation of the septohippocampal cholinergic system and that TF ameliorated learning and memory deficits partly through its increasing the central cholinergic activity. Therefore, TF could represent a potentially useful agent that is able to improve the function of impaired cognitive processes.

Post-traumatic stress disorder (PTSD) is a traumatic stress-related psychiatric disorder stimulated by experience. Green tea has potent antioxidative properties, due, in part, to the catechin (−) epigallocatechin-3-gallate (EGCG). EGCG is an important polyphenol with advantageous effects on anxiety and depression. Nevertheless, the mechanism about the inhibition of PTSD-like symptoms of EGCG is still unidentified. We examined whether EGCG improved learning and memory deficit stimulated in rats after single prolonged stress (SPS). Rats were administrated intraperitoneally (i.p.) with EGCG for 14 successive days after the SPS process. The SPS procedure stimulated cognitive deficit in the Morris water maze test and the object recognition task, and this impairment was improved by EGCG (25 mg/kg, i.p.). Daily EGCG administration significantly decreased the freezing response to contextual fear conditioning. The administration of EGCG also significantly moderated memory-related decreases in the alternation of cAMP-response element-binding protein and brain-derived neurotrophic factor in the hippocampus. Our results suggest that EGCG alleviated SPS-stimulated learning and memory deficit by inhibiting the increase of neuroinflammation in the rat brain. In addition, EGCG reversed the alternation of allopregnanolone and progesterone in the brain, and diminished simultaneously the hypothalamic–pituitary–adrenal axis dysfunction. Thus, EGCG reversed learning and memory-related behavioral dysfunction and molecular alternation accelerated by traumatic stress and may be a useful therapeutic material for PTSD. [ABSTRACT FROM AUTHOR]

Neuroinflammation is deliberated a major factor in various neurodegenerative diseases. Gypenosides (GPS) have pharmacological properties with multiple beneficial effects including anti-inflammatory, antioxidative, and protective properties. In the present study, whether GPS could improve cognitive dysfunction and chronic inflammation caused by injecting lipopolysaccharide (LPS) in the hippocampus was investigated. Effects of GPS on inflammatory factors in the hippocampus and the downstream mechanisms of these effects were also examined. Induction of LPS into the lateral ventricle caused inflammatory reactions and memory impairment on the rats. Every day treatment of GPS (25, 50, and 100 mg/kg) for 21 consecutive days attenuated spatial recognition, discrimination, and memory deficits. GPS treatment significantly decreased proinflammatory mediators such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and nuclear factor-kappaB (NF-κB) levels in the brain. Furthermore, GPS reduced LPS-induced elevated levels of inducible nitric oxide synthase (iNOS) and toll-like receptor 4 (TLR4) mRNA and inhibition of brain-derived neurotrophic factor (BDNF) mRNA level. Collectively, these results showed that GPS may improve cognitive function and provide a potential therapy for memory impairment caused by neuroinflammation. Based on these, GPS may be effective in inhibiting the progress of neurodegenerative diseases by improving memory functions due to its anti-inflammatory activities and appropriate modulation of NF-κB/iNOS/TLR4/BDNF. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a stress-related psychiatric/mental condition. Tangeretin (TAN), a major polymethoxylated flavone of citrus plants, exhibits anti-inflammatory and neuroprotective activities. However, whether TAN leads to cognitive improvement in PTSD patients remains unclear. In the present study, we explored whether TAN improved cognitive impairment induced in rats by single prolonged stress (SPS episode mimicking PTSD induction) and determined whether TAN reversed reductions in dopamine (DA) and serotonin (5-HT) levels. Rats were intraperitoneally injected with TAN for 14 consecutive days after the SPS, which had induced cognitive deficits evident in the object recognition task and the Morris water maze test; the impairments were improved by TAN (100 mg/kg). TAN rescued the neurochemical abnormalities and the SPS-induced decreases in DA and 5-HT levels in the hippocampus and amygdala. These effects may be attributable in part to induction of hippocampal genes encoding tyrosine hydroxylase and tryptophan hydroxylase-1. Our results support the idea that rats with PTSD exhibit changes in DAergic and serotonergic transmission and in memory impairment. Thus, TAN mediated reversal of memory-related behavioral dysfunction associated with traumatic stress may be a useful therapeutic intervention in PTSD patients. [ABSTRACT FROM AUTHOR]

A considerable number of patients with breast cancer complain of cognitive impairment after chemotherapy. In this study, we showed that donepezil enhanced memory function and increased brain glucose metabolism in a rat model of cognitive impairment after chemotherapy using behavioral analysis and positron emission tomography (PET). We found that chemotherapy affected spatial learning ability, reference memory, and working memory and that donepezil improved these cognitive impairments. According to PET analysis, chemotherapy reduced glucose metabolism in the medial prefrontal cortex and hippocampus, and donepezil increased glucose metabolism in the bilateral frontal lobe, parietal lobe, and hippocampus. Reduced glucose metabolism was more prominent after treatment with doxorubicin than cyclophosphamide. Our results demonstrated the neural mechanisms for cognitive impairment after chemotherapy and show that cognition was improved after donepezil intervention using both behavioral and imaging methods. Our results suggested that donepezil can be employed clinically for the treatment of cognitive deficits after chemotherapy. [ABSTRACT FROM AUTHOR]

We examined whether a crude methanol extract ofAngelica gigas(AgMx) improved the spatial cognitive impairment induced by repeated immobilization (IMO) stress in rats. The effects of AgMx on hippocampal expression of brain-derived neurotrophic factor (BDNF) and cAMP-response element-binding protein (CREB) were also investigated. For 21 days, male rats received daily doses of AgMx (20, 50, or 100 mg/kg, i.p.) 30 min prior to daily exposure to IMO stress (6 h/day). The daily administration of AgMx improved memory impairment, as measured by the passive avoidance test, and reduced the escape latency for finding the platform in the Morris water maze test. Additionally, as assessed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis, the administration of AgMx significantly alleviated memory-associated decreases in the expression levels of BDNF and CREB proteins and mRNAs in the hippocampus. Thus, these findings suggest that AgMx may be useful as a therapeutic agent in various neurodegenerative diseases for improving cognitive function. It effects likely involve the regulation of BDNF and CREB expressions. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine whether Phellodendri Cortex extract (PCE) could improve learning and memory impairments caused by lipopolysaccharide (LPS)-induced inflammation in the rat brain. The effect of PCE on modulating pro-inflammatory mediators in the hippocampus and its underlying mechanism were investigated. Injection of LPS into the lateral ventricle caused acute regional inflammation and subsequent deficits in spatial learning ability in the rats. Daily administration of PCE (50, 100, and 200 mg/kg, i.p.) for 21 days markedly improved the LPS-induced learning and memory disabilities in the Morris water maze and passive avoidance test. PCE administration significantly decreased the expression of pro-inflammatory mediators such as tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 mRNA in the hippocampus, as assessed by RT-PCR analysis and immunohistochemistry. Together, these findings suggest that PCE significantly attenuated LPS-induced spatial cognitive impairment through inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggested that PCE may be effective in preventing or slowing the development of neurological disorders, including Alzheimer's disease, by improving cognitive and memory function because of its anti-inflammation activity in the brain. [ABSTRACT FROM AUTHOR]

Background Alzheimer׳s disease (AD) is the most common cause of dementia. This disease is a progressive and irreversible brain disorder accompanied with severe learning and memory impairment. This study investigated whether treatment with standardized Lycii Fructus Extract (LFE) would improve the cognitive function and the pathological features of AD in 3xTg-AD mice. Ethnopharmacological relevance Lycii Fructus is a fruit of Lycium chinense Miller and widely distributed in East Asia and has been used traditionally for anti-aging purposes. Materials and methods The cognitive function of 3xTg-AD mice was assessed using the Morris water maze test. The levels of the amyloid beta deposits and NeuN in the hippocampus were evaluated with immunohistochemistry. Brain neurotrophic derived factor (BDNF) and tyrosine kinase B (TrkB) expressions were examined by western blot analysis. Results LFE treatment significantly ameliorated learning and memory deficits in AD mice, as shown by increased time spent in the target zone during probe tests. In addition, LFE significantly decreased Aβ deposits, increased NeuN-positive cells, and upregulated the expression of BDNF and TrkB in the 3xTg AD mice. Conclusions The present study suggests that LFE treatment can be a useful strategy for treating memory impairment induced by several neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Recently, lecithin-derived phosphatidylserine (PS), which originates from marine life, has received much attention as a viable alternative to bovine cerebral cortex PS. In this study, the use of squid phosphatidylcholine-transphosphatidylated PS (SQ-PS) was evaluated through examination of its ameliorating effects on age-associated learning and memory deficits in rats. Aged rats were orally administered SQ-PS (10, 20, or 50 mg/kg per day) once a day for seven days 30 min prior to behavioral assessment in a Morris water maze. SQ-PS administration produced significant dose-dependent improvements in escape latency for finding the platform in the Morris water maze in the aged rats even though Soy-PS administration also exhibited comparable improvements with SQ-PS. Biochemical alterations in the hippocampal cholinergic system, including changes in choline acetyltransferase and acetylcholinesterase immunoreactivity, were consistent with the behavioral results. In addition, SQ-PS treatment significantly restored age-associated decreases of choline transporter and muscarinic acetylcholine receptor type 1 mRNA expression in the hippocampus. These results demonstrate that orally administered SQ-PS dose-dependently aids in the improvement of memory deficits that occur during normal aging in rats. This suggests that SQ-PS may be a useful therapeutic agent in the treatment of diminished memory function in elderly people. [ABSTRACT FROM AUTHOR]