Resveratrol Produces Neurotrophic Effects on Cultured Dopaminergic Neurons through Prompting Astroglial BDNF and GDNF Release

Feng Zhang,Hang Liu,Jie Liu,Jing-Shan Shi,Yan-Ying Wang,Yuan-Fu Lu,Qin Wu

doi:10.1155/2012/937605

Abstract

Increasing evidence indicated astroglia-derived neurotrophic factors generation might hold a promising therapy for Parkinson's disease (PD). Resveratrol, naturally present in red wine and grapes with potential benefit for health, is well known to possess a number of pharmacological activities. Besides the antineuroinflammatory properties, we hypothesized the neuroprotective potency of resveratrol is partially due to its additional neurotrophic effects. Here, primary rat midbrain neuron-glia cultures were applied to investigate the neurotrophic effects mediated by resveratrol on dopamine (DA) neurons and further explore the role of neurotrophic factors in its actions. Results showed resveratrol produced neurotrophic effects on cultured DA neurons. Additionally, astroglia-derived neurotrophic factors release was responsible for resveratrol-mediated neurotrophic properties as evidenced by the following observations: (1) resveratrol failed to exert neurotrophic effects on DA neurons in the cultures without astroglia; (2) the astroglia-conditioned medium prepared from astroglia-enriched cultures treated with resveratrol produced neurotrophic effects in neuron-enriched cultures; (3) resveratrol increased neurotrophic factors release in the concentration- and time-dependent manners; (4) resveratrol-mediated neurotrophic effects were suppressed by blocking the action of the neurotrophic factors. Together, resveratrol could produce neurotrophic effects on DA neurons through prompting neurotrophic factors release, and these effects might open new alternative avenues for neurotrophic factor-based therapy targeting PD.

Highlights

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases characterized by a selective dopamine (DA) neuronal loss in the substantia nigra (SN) of the ventral midbrain
Rat primary midbrain neuron-glia cultures were treated with resveratrol (25–100 μM) on the first day
The [3H] DA uptake assay indicated that resveratrol treatment increased the capacity of dopaminergic neurons to take up DA by approximately 160% compared with the control cultures (Figure 1(a))

Summary

Introduction

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases characterized by a selective dopamine (DA) neuronal loss in the substantia nigra (SN) of the ventral midbrain. Astroglia are known to serve a number of housekeeping functions, such as the maintenance of the extracellular environment and the stabilization of neuron and glial cells communications in the brain [5]. Astroglia are the major source of various neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) [6]. It has become increasingly evident that neurotrophic factors are indispensable for the maintenance and neuronal protection in the developing and adult brain [7]. Lack of neurotrophic factors resulted in the neuronal loss and the progression of neurodegenerative diseases [8, 9]. Astroglial neurotrophic factors generation might hold a promising therapeutic potential for the treatment of neurodegenerative diseases

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Results

Conclusion