Background: Ethanol-induced neuronal apoptosis causes brain shrinkage and cognitive defects. Results: Exposure to ethanol (0.5% v/v for 72 h) in SH-SY5Y cells induced expression of miR-497 and miR-302b and downregulated expression of BCL2 and/or cyclin D2. Conclusion: Ethanol-induced neuronal apoptosis follows both the mitochondria-mediated and non-mitochondria-mediated pathways. Significance: Our study shows that miRNAs are involved in regulation of ethanol neurotoxicity.

The generation of differentiated and functional neurons is a complex process, which requires coordinated expression of several proteins and microRNAs (miRNAs). The present study using nerve growth factor (

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The plethora of literature has supported the potential benefits of Resveratrol (RV) as a life-extending as well as an anticancer compound. However, these two functional discrepancies resulted at different concentration ranges. Likewise, the role of Resveratrol on adult neurogenesis still remains controversial and less understood despite its well documented health benefits. To gather insight into the biological effects of RV on neurogenesis, we evaluated the possible effects of the compound on the proliferation and survival of neural progenitor cells (NPCs) in culture, and in the hippocampus of aged rats. Resveratrol exerted biphasic effects on NPCs; low concentrations (10 μM) stimulated cell proliferation mediated by increased phosphorylation of extracellular signal-regulated kinases (ERKs) and p38 kinases, whereas high concentrations (>20 μM) exhibited inhibitory effects. Administration of Resveratrol (20 mg/kg body weight) to adult rats significantly increased the number of newly generated cells in the hippocampus, with upregulation of p-CREB and SIRT1 proteins implicated in neuronal survival and lifespan extension respectively. We have successfully demonstrated that Resveratrol exhibits dose dependent discrepancies and at a lower concentration can have a positive impact on the proliferation, survival of NPCs and aged rat hippocampal neurogenesis implicating its potential as a candidate for restorative therapies against age related disorders.

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The role of resveratrol (RV), a natural polyphenol, is well documented, although its role on neurogenesis is still controversial and poorly understood. Therefore, to decipher the cellular insights of RV on neurogenesis, we investigated the potential effects of the compound on the survival, proliferation, and neuronal differentiation of human cord blood-derived mesenchymal stem cells (hCBMSCs). For neuronal differentiation, purified and characterized hCBMSCs were exposed to biological safe doses of RV (10 μM) alone and in combination with nerve growth factor (NGF-50 ng). The cells exposed only to NGF (50 ng/mL) served as positive control for neuronal differentiation. The genes showing significant involvement in the process of neuronal differentiation were further funneled down at transcriptional and translational level. It was observed that RV promotes PKA-mediated neuronal differentiation in hCBMSCs by inducing canonical pathway. The studies with pharmacological inhibitors also confirmed that PKA significantly induces β-catenin expression via GSK3β induction and stimulates CREB phosphorylation and pERK1/2 induction. Besides that, the studies also revealed that RV additionally possesses the binding sites for molecules other than PKA and GSK3β, with which it interacts. The present study therefore highlights the positive impact of RV over the survival, proliferation, and neuronal differentiation in hCBMSCs via PKA-mediated induction of GSK3β, β catenin, CREB, and ERK1/2.

Differentiating neuronal cells derived from human umbilical cord blood stem cells have been used as an in vitro tool for the assessment of developmental neurotoxicity of monocrotophos (MCP), an organophosphate pesticide. The differentiating cells were exposed to MCP during the different stages of maturation, viz., days 2, 4, and 8, and changes in the makers of cell proliferation, neuronal differentiation, neuronal injuries, and receptors were studied. We found significant upregulation in the different MAPKs, apoptosis, and neurogenesis markers and downregulation in the cell proliferation markers during neuronal differentiation. We further identified significant upregulation in the expression of different MAPKs and proteins involved in oxidative stress, apoptosis, and calpain pathways in the mid-differentiating cells exposed to MCP. The upregulated levels of these proteins seem to be the main cause of alteration during the differentiation process towards apoptosis as a fine-tune of pro-apoptotic and anti-apoptotic proteins are desirable for the process of differentiation without apoptosis. The decreased acetylcholinesterase activity, dopaminergic, and cholinergic receptors and increased acetylcholine levels in the differentiating neuronal cells indicate the vulnerability of these cells towards MCP-induced neurotoxicity. Our data confirms that differentiating neuronal cells derived from human umbilical cord stem cells could be used as a powerful tool to assess the developmental neurotoxicity in human beings.

The critical role of serotonin (5-hydroxytryptamine; 5-HT) and its receptors (5-HTRs) in the pathophysiology of diverse neuropsychiatric and neurodegenerative disorders render them attractive diagnostic and therapeutic targets for brain disorders. Therefore, the in vivo assessment of binding of 5-HT receptor ligands under a multitude of physiologic and pathologic scenarios may support more-accurate identification of disease and its progression and the patient's response to therapy as well as the screening of novel therapeutic strategies. The present Review aims to focus on the current status of radioligands used for positron-emission tomography (PET) and single-photon-emission computerized tomography (SPECT) imaging of human brain serotonin receptors. We further elaborate upon and emphasize the attributes that qualify a radioligand for theranostics on the basis of its frequency of use in clinics, its benefit to risk assessment in humans, and its continuous evolution, along with the major limitations.