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Over the past two decades, the prevalence of Autism Spectrum Disorder (ASD) has become a very crucial issue. Therefore, understanding the causes and risk factors of ASD is important, and many researchers have focused on analyzing its factors. Valproic Acid (VPA), a drug used for treating neural and psychiatric disorders, has been implicated in increasing ASD risk when exposure occurs in utero. Even though there is evidence linking VPA to ASD-like behaviors in animal models, the biological mechanisms remain still unclear. This study aims to elucidate these mechanisms by analyzing gene expression changes in human neuron cells treated with VPA. We performed cell viability assays to determine the cytotoxic concentration of VPA. Also, we conducted RNA sequencing (RNA-Seq) to analyze the gene expression of non-treated control and VPA-treated cells. Our experimental results reveal that VPA induces significant changes in gene expression levels in human brain cells. The experimental result provides a new insight into how VPA exposure contributes to ASD phenotypes. By identifying differentially expressed genes and their associated biological processes and cellular functions, this research enhances our understanding of the molecular impacts of VPA on neuronal development. In conclusion, this research paper focused on potentially guiding future therapeutic strategies for ASD. [ABSTRACT FROM AUTHOR]

Class II histone deacetylases (HDACs) are considered as potential targets to treat Alzheimer's disease (AD). Previously, C-3 substituted phenothiazine-containing compounds with class II HDAC-inhibiting activities was found to promote neurite outgrowth. This study replaced phenothiazine moiety with phenoxazine that contains many C-3 and C-4 substituents. Some resulting compounds bearing the C-4 substituent on a phenoxazine ring displayed potent class II HDAC inhibitory activities. Structure-activity relationship (SAR) of these compounds that inhibited HDAC isoenzymes was disclosed. Molecular modelling analysis demonstrates that the potent activities of C-4 substituted compounds probably arise from π-π stacked interactions between these compounds and class IIa HDAC enzymes. One of these, compound 7d exhibited the most potent class II HDAC inhibition (IC50= 3–870 nM). Notably, it protected neuron cells from H2O2-induced neuron damage at sub-μM concentrations, but with no significant cytotoxicity. These findings show that compound 7d is a lead compound for further development of anti-neurodegenerative agents. [ABSTRACT FROM AUTHOR]

Class II histone deacetylases (HDACs) are considered as potential targets to treat Alzheimer’s disease (AD). Previously, C-3 substituted phenothiazine-containing compounds with class II HDAC-inhibiting activities was found to promote neurite outgrowth. This study replaced phenothiazine moiety with phenoxazine that contains many C-3 and C-4 substituents. Some resulting compounds bearing the C-4 substituent on a phenoxazine ring displayed potent class II HDAC inhibitory activities. Structure-activity relationship (SAR) of these compounds that inhibited HDAC isoenzymes was disclosed. Molecular modelling analysis demonstrates that the potent activities of C-4 substituted compounds probably arise from π-π stacked interactions between these compounds and class IIa HDAC enzymes. One of these, compound 7d exhibited the most potent class II HDAC inhibition (IC50= 3–870 nM). Notably, it protected neuron cells from H2O2-induced neuron damage at sub-μM concentrations, but with no significant cytotoxicity. These findings show that compound 7d is a lead compound for further development of anti-neurodegenerative agents.

Serum and glucocorticoid-regulated kinase 1 (SGK1) is expressed in neuronal cells and involved in the pathogenesis of hypertension and metabolic syndrome, regulation of neuronal function, and depression in the brain. This study aims to identify the cellular mechanisms and signaling pathways of SGK1 in neuronal cells. In this study, the SGK1 inhibitor GSK650394 is used to suppress SGK1 expression in PC12 cells using an in vitro neuroscience research platform. Comparative transcriptomic analysis was performed to investigate the effects of SGK1 inhibition in nervous cells using mRNA sequencing (RNA-seq), differentially expressed genes (DEGs), and gene enrichment analysis. In total, 12,627 genes were identified, including 675 and 2152 DEGs at 48 and 72 h after treatment with GSK650394 in PC12 cells, respectively. Gene enrichment analysis data indicated that SGK1 inhibition-induced DEGs were enriched in 94 and 173 genes associated with vascular development and functional regulation and were validated using real-time PCR, Western blotting, and GEPIA2. Therefore, this study uses RNA-seq, DEG analysis, and GEPIA2 correlation analysis to identify positive candidate genes and signaling pathways regulated by SGK1 in rat nervous cells, which will enable further exploration of the underlying molecular signaling mechanisms of SGK1 and provide new insights into neuromodulation in cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background. Brain edema is swelling in the brain due to excessive accumulation of fluid in the brain. This condition is triggered by a decrease in cerebral blood flow (CBF) due to heart damage or isoproterenol administraion. A decrease in CBF results in brain edema which triggers damage to neuron cells. This study uses isoproterenol to induce brain edema. This damage is prevented by giving ramipril with the aim of improving cardiac and brain perfusion. Objective. To see the effect of giving ramipril to the microscopic assessment of mouses brain neuron cells with brain edema which was induced by isoproterenol. Methods. This research is an experimental study which was used 21 experimental animals which were divided into 3 groups (K-, K +, and P). The treatment group (P) was given ramipril at a dose of 3 mg/KgBW for 7 days. On the 8th and 9th day K+ and P groups were injected by isoproterenol 85 mg/KgBW to induce brain edema through AMI. Data analysis was performed using the Kruskal-Wallis Test and Mann Whitney U Test (MWUT). Results. The average number of neuron cell damage in the K -, K +, and P group, respectively, 6.2, 26.3 and 17.33. Significant differences were obtained for each group with a value of p = 0.001 (p

We evaluated the neuroprotective effect of L-theanine in Parkinson's disease and the underlying mechanism focusing on WNT/β-catenin signaling mediated by the MAPK pathway. We treated MPTP-induced SH-SY5Y cells with various concentrations of L-theanine (50, 100, 200, and 500 μg/mL), and we also treated Parkinson's model mice with L-theanine. L-theanine treatment effectively reduced the immunohistochemical hallmarks of Parkinson's disease, particularly Lewy bodies and α-synuclein, and increased the number of tyrosine hydroxylase-positive cells. L-theanine also improved the motor dysfunction in MPTP-induced Parkinson's disease model mice as measured by the rotarod test. The levels of several pro-inflammatory mediators that are overexpressed in Parkinson's disease, namely TNF-α, IL-6, COX-2, and MAC-1, were reduced following L-theanine treatment, and the levels of the pro-apoptotic proteins Bcl-2, caspase-3, p53, and PARP-1 were significantly reduced. L-theanine regulated the oxidative stress-related factors SOD-1, GST, and NOX-4 by targeting several proteins related to WNT/β-catenin signaling, i.e., β-catenin, WNT-3a, WNT-5a, TCF1/TCF7, and LEF1, via the MAPK pathway (p -JNK, p -ERK, and p -p38). Our results indicate that L-theanine is neuroprotective and has anti-inflammatory effects that could be beneficial for treating Parkinson's disease. L-Theanine facilitated the neuroprotective effect by mediating the Wnt/b-catenin signaling pathways. L-theanine has activated both Wnt/β-catenin signaling and the MAPK signaling pathways, subsequently downregulating the pro-inflammation, apoptosis, and oxidative stress mediators and enhancing the motor function. [Display omitted] [ABSTRACT FROM AUTHOR]

While there is a growing interest in the use of statins, HMG-CoA reductase inhibitors, to treat neurodegenerative diseases, statins are associated with conflicting effects within the central nervous system (CNS) without clear evidence of the underlying mechanisms. This study systematically investigated effects of four statins (atorvastatin, pitavastatin, cerivastatin, and lovastatin) on neuronal cells under pathological condition using an in vitro model depicting ischemic injury, as well as tested under physiological condition. All four statins at micromolar concentrations display toxic effects on neuron cells under physiological condition. Atorvastatin and cerivastatin but not pitavastatin or lovastatin at nanomolar concentrations display protective effects on neuron cells under ischemic injury condition, via decreased ischemic injury-induced oxidative stress, oxidative damage, and inflammation. Mechanistically, atorvastatin, pitavastatin, and lovastatin induces neuron cell apoptosis via prenylation-independent manner. Other mechanisms are involved in the pro- apoptotic effect of cerivastatin. Prenylation is not involved in the protective effects of statins under ischemic injury condition. Our work provides better understanding on the multiple differential effects of statins on neuron cells under physiological condition and ischemic injury, and elucidate their underlying mechanisms, which may be of relevance to the influence of statins in CNS. [ABSTRACT FROM AUTHOR]

Serum and glucocorticoid-regulated kinase 1 (SGK1) is expressed in neuronal cells and involved in the pathogenesis of hypertension and metabolic syndrome, regulation of neuronal function, and depression in the brain. This study aims to identify the cellular mechanisms and signaling pathways of SGK1 in neuronal cells. In this study, the SGK1 inhibitor GSK650394 is used to suppress SGK1 expression in PC12 cells using an in vitro neuroscience research platform. Comparative transcriptomic analysis was performed to investigate the effects of SGK1 inhibition in nervous cells using mRNA sequencing (RNA-seq), differentially expressed genes (DEGs), and gene enrichment analysis. In total, 12,627 genes were identified, including 675 and 2152 DEGs at 48 and 72 h after treatment with GSK650394 in PC12 cells, respectively. Gene enrichment analysis data indicated that SGK1 inhibition-induced DEGs were enriched in 94 and 173 genes associated with vascular development and functional regulation and were validated using real-time PCR, Western blotting, and GEPIA2. Therefore, this study uses RNA-seq, DEG analysis, and GEPIA2 correlation analysis to identify positive candidate genes and signaling pathways regulated by SGK1 in rat nervous cells, which will enable further exploration of the underlying molecular signaling mechanisms of SGK1 and provide new insights into neuromodulation in cardiovascular diseases.

This study aimed to determine the function of motoric reflexes and memory as a result of the necrosis of neuron cells in the cerebellum of infant mice (Mus musculus) from their carbofuran exposed mothers during lactation periods. The decreased motoric reflexes as an indicator of the reduced memory ability and concentration ability in infant mice. This experimental laboratory study used 36 mice and carbofuran injected using gavage method with the fraction of LD50 in mother mice in the dose of 5 mg/kg body weight (BW). The mother mice were exposed with carbofuran during lactation period from Day 0 to Day 9 and the 10-days-old infant mice were then terminated for microscopic examination by counting the necrosis of neuron cell by applying HE staining and the motoric-reflex function tests (neurobehavioral test) on the 10-days-old infant mice which included: surface righting reflexes, swimming and a memory test employing an Eight-arm radial maze at 20 days-old. The calculation results were analyzed using the Kruskal-Wallis test and the Mann Whitney test. The results of this study showed a significant increase in the necrosis of neuron cell, a fundamental decreased motoric reflex in infant mice in these activities; such as surface righting reflex and swimming ability (the head angle position and swimming direction) and eight-arm radial maze memory test. Conclusion: in sum, the exposure of carbofuran in the mother mice during lactation period causes the increase in necrosis of neuron cell, the decrease of motoric reflexes and the memory ability for infant mice. [ABSTRACT FROM AUTHOR]

Rapid and accurate purification of various heterogeneous mixtures is a critical step for a multitude of molecular, chemical, and biological applications. Dielectrophoresis has shown to be a promising technique for particle separation due to its exploitation of the intrinsic electrical properties, simple fabrication, and low cost. Here, we present a geometrically novel dielectrophoretic channel design which utilizes an array of localized electric fields to separate a variety of unique particle mixtures into distinct populations. This label‐free device incorporates multiple winding rows with several nonuniform structures on to sidewalls to produce high electric field gradients, enabling high locally generated dielectrophoretic forces. A balance between dielectrophoretic forces and Stokes' drag is used to effectively isolate each particle population. Mixtures of polystyrene beads (500 nm and 2 μm), breast cancer cells spiked in whole blood, and for the first time, neuron and satellite glial cells were used to study the separation capabilities of the design. We found that our device was able to rapidly separate unique particle populations with over 90% separation yields for each investigated mixture. The unique architecture of the device uses passivated‐electrode insulator‐based dielectrophoresis in an innovative microfluidic device to separate a variety of heterogeneous mixture without particle saturation in the channel. [ABSTRACT FROM AUTHOR]

The loss of bonding attachments to maternal deaths as a cause of neonatal stress had an impact on brain growth and development in early life. HPA axis activation responsed to secrete corticotropin releasing hormone which stimulated adrenocorticotropic hormonessecretion. These hormones induced the adrenal gland cortex to secrete glucocorticoids. Excessive release of glucocorticoids would suppress BDNF expression resulting in BDNF hypofunction resulting in neuronal cell apoptosis which was characterized by an increase in neuronal cell apoptosis index. This study aimed to analyze the apoptosis index of neuron cells in the cerebrum and cerebellum of newborn Rattus norvegicus that were not separated from the mother until 3 days old as the control group (K1) and the cerebrum and cerebellum of newborn Rattus norvegicus that were separated from the mother by giving animal milk as replacement nutrition until 3 days old as a group treatment (K2). 3 Rattus norvegicus newborn with heaviest, medium, and lowest weights were taken from each mother then sacrificed for the brain histochemical preparations. Imonohistochemical examination was carried out to calculate the neuronal apoptosis index. The analysis results showed that the apoptotic index of neuron cells in the cerebellum and cerebellum of newborn Rattus norvegicus which separated from the mother were higher than those not separated from the mother. [ABSTRACT FROM AUTHOR]

Abstract Background aims Degeneration of the central nerve system, particularly in Alzheimer's disease, is a burden on society, and despite years of research, there is no effective treatment. Cell therapy appears to be an option that is of growing interest in neural studies. The main aim of this study was to investigate the histological and physiological effects of transplantation the neuron-like cell (NLC)-derived mouse embryonic stem cells (mESCs) on the repair of brain lesions in an Alzheimer's animal model (AM) in rats. Methods Behavioral experiments were conducted in the light hours in a Y-shaped maze device. Animals were randomly divided into five groups, with seven rats per group. The nucleus basalis of Meynert (NBM) was destroyed bilaterally with an electrical lesion (0.5 mA for 3 s). One week after the bilateral lesion of the NBM, the differentiated NLCs (0.1 mL) were injected with stereotaxic surgery using a Hamilton syringe at NBM coordinates, and behavioral and histological tests were performed by the Y-maze task and hematoxylin and eosin staining after five weeks of the lesion. Also, differentiated cells detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis and fluorescent immunostaining. Results The expression of neuronal markers including Nestin, Map2, NF-H, Tuj-1, GFAP and Olig-2 was surveyed by using the immunocytochemistry and qRT-PCR methods, and the results confirmed that the genes in question were expressed significantly more compared than the control sample. Five weeks after the cell transplantation in the AM, morphological and physiological investigation during the determination period confirmed improved disease state in the tested models. Conclusions It should be noted that by improving the neuronal connectivity in AM rat brains, the transplanted NLCs rescue Alzheimer's cognition. This research has presented some preclinical evidence that showed NLCs transplantation can be used for AM treatment. [ABSTRACT FROM AUTHOR]

Retinal stem cells (RSCs) have been defined as neural cells with the potential to self-renew and to generate all the different cell types of the nervous system following differentiation, which are an ideal engraft in retinal regeneration. In this research, mouse RSCs were isolated from retina, induced differentiation into neuron cellsin vitroafter over-expression of miR-9. The results showed that the RSCs could induce differentiation into neuron cells under the special medium, but when the miR-9 was over-expressed, the differentiated efficiency of neuron cells from RSCs could be promoted. This reason was demonstrated that polypyrimidine tract-binding protein 1 (PTBP1) was a repressor for polypyrimidine tract-binding protein 2 (PTBP2), during neuronal differentiation, miR-9 reduced PTBP1 levels, leading to the accumulation of correctly spliced PTBP2 mRNA and a dramatic increase in PTBP2 protein. And then miR-9 promoted neuron cells from RSCs were successful colonized into injured spinal cord for participation in tissue-repair. In conclusion, our research showed that the miR-9 promoted the differentiation of neuronal cells from RSCs, and this mechanism was miR-9 reduced the expression of PTBP1, increased the expression of PTBP2. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) is an addictive drug that can cause toxicity and degeneration in the brain. Several pieces of evidence have demonstrated that METH toxicity results in increases in oxidative stress that regulate an intracellular signaling cascade that leads to cell death. Recently, several studies have emphasized that the overload of cytosolic calcium levels and mitochondrial fission into a small mitochondrial structure is involved in cell death processes. In the present study, we aimed to investigate the effects of METH toxicity on cytosolic calcium overload and mitochondrial fission in neuroblastoma SH-SY5Y cells. Additionally, the protective effect of melatonin against METH-induced toxicity was also investigated. The results of the present study demonstrated that METH significantly decreases cell viability and increases the levels of mitochondrial fission (Fis1 and Drp1) proteins and pro-apoptotic protein, Bax in isolated mitochondria. The levels of Drp1 in the cytosol of METH-treated cells had no significant differences compared to the control untreated cells. METH also significantly increased the cytosolic calcium levels. Melatonin reversed the toxic effects of METH by restoring cell viability and inhibiting the increase in mitochondrial Fis1 levels and the mitochondrial translocation of Drp1 and Bax. Additionally, melatonin was able to reduce the METH-induced increase in cytosolic calcium levels and fragmented mitochondria into small globular structures in SH-SY5Y cells. The results of the present study demonstrate the potential abilities of melatonin to maintain the homeostasis of mitochondrial dynamics and cytosolic calcium levels in METH-induced toxicity in neuronal cells. [ABSTRACT FROM AUTHOR]

7‑Methoxyheptaphylline (7‑MH) is a carbazole extracted from Clausena harmandiana , a medicinal plant that is used to treat headaches and stomachaches. The aim of the present study was to examine the neuroprotective effects and anticancer activity of 7‑MH. Cell death was assessed using an MTT assay and flow cytometry. The expression of apoptosis‑related proteins was determined by western blot analysis. An animal model was used to test anti‑metastasis. The interactions between 7‑MH and the molecular target were observed using molecular docking. The results revealed that 7‑MH provided protection against hydrogen peroxide (H 2 O 2 )‑induced neuronal cell death. In cancer cells, 7‑MH induced SH‑SY5Y, 4T1, HT29, HepG2, and LNCaP cell death. 7‑MH inhibited metastasis of HT29 cells in vitro and 4T1‑Luc cells in vitro and in vivo . 7‑MH inhibited proteins, including P‑glycogen synthase kinase (GSK)‑3, and cleaved caspase‑3, but it activated anti‑apoptotic proteins in H 2 O 2 ‑induced SH‑SY5Y cell death. By contrast, 7‑MH activated the cleaving of caspase‑3 and GSK‑3, but it suppressed anti‑apoptotic proteins in SH‑SY5Y cells. 7‑MH reduced the levels of NF‑κB and STAT3 in 4T1 cells; phospho‑p65, Erk, and MAPK13 in LNCaP cells; and phospho‑Erk and matrix metalloproteinase‑9 in HT29 cells. Molecular docking analysis showed that 7‑MH targets TAK1 kinase. The present study indicated that 7‑MH induced apoptosis of cancer cells and provided protection against H 2 O 2 ‑induced neuron cell death via TAK1 kinase.

Highlights: [•] A new pyrazoline-based turn-on fluorescence probe toward Zn2+ was synthesized. [•] Upon addition of Zn2+, the fluorescence intensity was enhanced up to 80-fold. [•] The fast response to Zn2+ makes the probe suitable to monitor Zn2+ in living cell. [Copyright &y& Elsevier]

Objective: To investigate the effect and mechanism of piceatannol on cerebral ischemia-reperfusion injury., Methods: The oxygen-glucose deprivation reperfusion (OGD/R) model was constructed in primary cultured suckling rat cortical neuron cells. After 2 h of oxygen-glucose deprivation, the cells were treated with piceatannol for 24 h. The cell survival rate was detected by MTT assay, and the degree of cell damage was detected by intracellular lactate dehydrogenase (LDH) release assay. The activity of superoxide dismutase (SOD) and the content of adenosine triphosphate (ATP) were detected by colorimetric method. The content of reactive oxygen species (ROS) was detected by flow cytometry or observed with inverted fluorescence microscope. The ultrastructure of mitochondria was observed with transmission electron microscopy. Western blotting was used to detect the phosphorylation levels of protein kinase B (AKT) and glycogen synthase kinase (GSK)-3β. Immunofluorescence staining was used to observe the nuclear localization of nuclear factor-erythroid 2-related factor (Nrf) 2. After OGD/R neuron cells were pretreated with Nrf2 inhibitor ML385 for 24 h, the effect of Nrf2 on the improvement of cell activity and antioxidant activity of piceatannol were investigated. Western blotting was used to detect the protein expression levels of Nrf2, heme oxygenase (HO) 1 and NADPH quinone oxidoreductase (NQO) 1., Results: Piceatannol significantly increased the survival rate of OGD/R neurons, decreased LDH release and reactive oxygen species content, increased SOD activity, ameliorated mitochondrial ultrastructural damage, increased mitochondrial membrane potential and ATP level (all P <0.05), increased phosphorylation of AKT and GSK-3β protein, up-regulated the expression of Nrf2, HO-1 and NQO1 protein, increased the nuclear-to-plasma ratio of Nrf2, and promoted the nuclear transfer of Nrf2 (all P <0.05). ML385 could significantly reverse the rescue effect of paclitaxel on the model cells and the regulatory activities of SOD, ROS and LDH (all P <0.05)., Conclusion: Piceatannol can regulate Nrf2 by activating GSK-3β signaling pathway, promote its nuclear translocation, exert corresponding antioxidant effect, and protect mitochondrial structure and function in rat neuron cells.

While there is a growing interest in the use of statins, HMG-CoA reductase inhibitors, to treat neurodegenerative diseases, statins are associated with conflicting effects within the central nervous system (CNS) without clear evidence of the underlying mechanisms. This study systematically investigated effects of four statins (atorvastatin, pitavastatin, cerivastatin, and lovastatin) on neuronal cells under pathological condition using an in vitro model depicting ischemic injury, as well as tested under physiological condition. All four statins at micromolar concentrations display toxic effects on neuron cells under physiological condition. Atorvastatin and cerivastatin but not pitavastatin or lovastatin at nanomolar concentrations display protective effects on neuron cells under ischemic injury condition, via decreased ischemic injury-induced oxidative stress, oxidative damage, and inflammation. Mechanistically, atorvastatin, pitavastatin, and lovastatin induces neuron cell apoptosis via prenylation-independent manner. Other mechanisms are involved in the pro-apoptotic effect of cerivastatin. Prenylation is not involved in the protective effects of statins under ischemic injury condition. Our work provides better understanding on the multiple differential effects of statins on neuron cells under physiological condition and ischemic injury, and elucidate their underlying mechanisms, which may be of relevance to the influence of statins in CNS., (© 2022 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

The article discusses a study which isolated inner cell mass from hatched and expanded blastocysts on day 8 and 9 to generate (buffalo embryonic stem) BuES cell-like cells and establish its differential potential in vitro by induced differentiation and embryoid body formation. It offers information on the materials and methods used including in vitro production of blastocysts and total cell number, isolation and culture of inner cell mass cells, and alkaline phosphatase staining.

Abstract: This paper reports the success of amino-functionalization on multi-walled carbon nanotubes (MWCNTs) to promote neuronal cells growth on MWCNT electrode for extracellular recording, attributed to the formation of positive charge of NH2 molecules on their surfaces. Besides, the surface of MWCNT electrode becomes hydrophilic after amino-functionalization (AF-MWCNTs) which can enhance electrical conductivity because of lower MWCNT/electrolyte interfacial impedance and higher interfacial capacitance. Durability tests show that electrical characteristics of the MWCNTs treated by 2wt% 1,4-diaminobutane solution (2wt%-AF-MWCNTs) can last for at least six months in air ambient. The neural recording of crayfish shows that 2wt%-AF-MWCNTs can provide better capability on detecting action potentials of caudal photoreceptor (CPR) interneuron compared to suction glass pipette from the evidence of a higher S/N ratio (126 versus 23). The amino-functionalized MWCNT electrode is feasible for long-term recording application according to the results of biocompatibility tests. As the MWCNTs were directly synthesized on Si-based substrates by catalyst-assisted thermal chemical vapor deposition (CVD) at a low temperature (400°C), these self-aligned MWCNT electrodes could be friendly implemented in integrated circuits fabrications. [Copyright &y& Elsevier]

Abstract: The neuroprotective effects of ergothioneine (EGT) against cisplatin toxicity were investigated both in vitro and in vivo. For in vitro study, two types of neuronal cells, primary cortical neuron (PCN) cells and rat pheochromocytoma (PC12) cells, were incubated with EGT (0.1–10.0μM) for 2h followed by incubation with 0.5μM cisplatin for 72h. Results show that cisplatin markedly decreased the proliferation of PC12 cells and strongly inhibited the growth of axon and dendrite of PCN cells, but these effects were significantly prevented by EGT. For in vivo study, CBA mice were orally administered with 2 or 8mg EGT/kgbody weight for 58 consecutive days and were injected i.p. with 5mg cisplatin/kgbody weight on days 7, 9 and 11. We found that EGT significantly restored the learning and memory deficits in mice treated with cisplatin evaluated by active and passive avoidance tests. EGT also significantly prevented brain lipid peroxidation, restored acetylcholinesterase (AChE) activity and maintained glutathione/glutathione disulfide ratio in brain tissues of mice treated with cisplatin. These results demonstrate that EGT protects against cisplatin-induced neuronal injury and enhances cognition, possibly through the inhibition of oxidative stress and restoration of AChE activity in neuronal cells. [ABSTRACT FROM AUTHOR]

The study investigated the neurotoxic effects and underlying mechanisms of aconitine on cerebral cortex neuron cells prepared from neonatal SD rats. The uniform design and MTT method were applied to study the effect of aconitine with different concentrations at scheduled time. The influence of aconitine at the maximal toxicity concentration was observed using optical microscope and electron microscope. The influences of aconitine on neuron cells membrane, neuron cells’ inner balance, energy metabolism and neurotransmitters were observed to investigate the action mechanisms of aconitine. The results indicated that the maximal toxicity-concentration was 2% and the critical time were 30 s, 1 min and 20 min respectively. The effects of aconitine on neuron cells’ morphology included cells synapse’s fracture, cells membrane fragment, mitochondria’s swell, cytoplasmic vacuoles, nuclear chromatin’s condensation and accumulation. The stability of biomembrane, the internal milieu and the energy metabolism were also disturbed with the increase of activity of LDH and concentration of neurotransmitters (acetylcholine, opioid, catecholamine and SP) in culture medium, the increase of the activity of ACP and [Na+], [Ca2+] concentration, and the decrease of Na+-K+-ATP, [K+], [Mg2+] and glycogen concentration in the cells. Toxic mechanisms of aconitine damaging neuron cells may be because it inhibited the activity of Na+-K+-ATP, influenced the concentrations of [Na+], [K+], [Ca2+], [Mg2+] and neurotransmitters in the cells, which resulted in the injuries of cells’ morphology and function. [ABSTRACT FROM AUTHOR]

We designed and synthesized a new pyrazoline-based turn-on fluorescence probe for Zn(2+) by the reaction of chalcone and thiosemicarbazide. The structure of the probe was characterized by IR, NMR and HRMS spectroscopy. The probe (L) exhibits high selectivity and sensitivity for detecting Zn(2+) in buffered EtOH/HEPES solution (EtOH/HEPES=1/1, pH 7.2) with 80-fold fluorescence enhancement, which is superior to previous reports. Job's plot analysis revealed 1:1 stoichiometry between probe L and Zn(2+) ions. The association constant estimated by the Benesi-Hildebrand method and the detection limit were 3.92×10(3)M(-1) and 5.2×10(-7)M, respectively. A proposed binding mode was confirmed by (1)H NMR titration experiments and density functional theory (DFT) calculations. The probe is cell-permeable and stable at the physiological pH range in biological systems. Because of its fast response to Zn(2+), the probe can monitor Zn(2+) in living cells. Moreover, the selective binding of L and Zn(2+) was reversible with the addition of EDTA in buffered EtOH/HEPES solution and Zn(2+) could be imaged in SH-SY5Y neuron cells., (Copyright © 2014 Elsevier B.V. All rights reserved.)