Abstract
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.
Highlights
Neural progenitor cells (NPCs) are defined as self-renewing, multipotent cells that generate neurons, astrocytes, and oligodendrocytes in the nervous system[1]
Rat brain neural progenitor cells (NPCs) isolated from embryonic day-12 (ED-12)
Considerable research has been directed towards identifying substances that mimic the physiological effects of calorie restriction, and RV has emerged as a leading candidate in this realm
Summary
Quantification of immunostained neurospheres with Nestin and SOX2 showed a significant increase in the expression of these markers in cultures exposed to RV (10 μM) (Fig. 7a–c) These findings indicate that lower concentrations of RV induce proliferation, while higher doses of RV are cytotoxic. Results showed that more BrdU positive cells were observed in RV-treated aged rats and its number was higher when compared to aged control rats These changes were associated with a significant increase in the neurogenesis marker NeuN in aged rats treated with RV (0.88 ±.03) as opposed to rats in the aged group (0.73 ±.04) (Fig. 14a,c). Treatment of RV significantly increased the expression of p-ERK1/2, p-p38, p-CREB and SIRT1 in both hippocampus and frontal cortex regions in comparison to aged control rats
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