Abstract
BackgroundMicroglia-mediated neuroinflammation is recognized to mainly contribute to the pathogenesis of Parkinson’s disease (PD). Tetrahydroxystilbene glucoside (TSG) has been proved to be beneficial for health with a great number of pharmacological properties. We examined the effects of TSG against dopamine (DA) neuronal loss towards development of a PD treatment strategy.MethodsSubstantia nigral stereotaxic single injection of lipopolysaccharide (LPS)-induced rat DA neuronal damage was employed to investigate TSG-produced neuroprotection. In addition, primary rat midbrain neuron-glia co-cultures were performed to explore the underlying mechanisms.ResultsDaily intraperitoneal injection of TSG for seven consecutive days significantly attenuated LPS-induced loss of DA neurons in the substantia nigra. In addition, glia-dependent mechanisms were responsible for TSG-mediated neuroprotection. First, TSG ameliorated microglia-mediated neuroinflammation and the subsequent production of various pro-inflammatory and neurotoxic factors. Second, astroglial neurotrophic factor neutralization weakened TSG-mediated neuroprotection, showing that TSG was protective in part via increasing astroglia-derived neurotrophic factor secretion.ConclusionsTSG protects DA neurons against LPS-induced neurotoxicity through dual modulation on glial cells by attenuating microglia-mediated neuroinflammation and enhancing astroglia-derived neurotrophic effects. These findings might open new alternative avenues for PD treatment.
Highlights
Microglia-mediated neuroinflammation is recognized to mainly contribute to the pathogenesis of Parkinson’s disease (PD)
Oxidative stress, and environmental exposure have been identified to be closely associated with the pathogenesis of PD, the mechanisms underlying the progressive feature of DA neurodegeneration are not fully elucidated
Tetrahydroxystilbene glucoside (TSG) produces neuroprotection against LPS-induced DA neurotoxicity Rat primary midbrain neuron-glia cultures were treated with TSG (20–80 μM) for 30 min before LPS (10 ng/ml) application
Summary
Microglia-mediated neuroinflammation is recognized to mainly contribute to the pathogenesis of Parkinson’s disease (PD). We examined the effects of TSG against dopamine (DA) neuronal loss towards development of a PD treatment strategy. Parkinson’s disease (PD) is among the most common and age-related neurodegenerative disease. It is characterized by slow and progressive loss of dopamine (DA) neurons in the midbrain substantia nigra (SN) and the consequent severe decrease of DA levels in the striatum. Current drug treatments are mainly focused on symptomatic controls and long-term application results in a loss of drug efficacy. Neuroinflammation is increasingly implicated in the pathogenesis of neurodegenerative diseases, such as PD, Alzheimer’s disease (AD), and Huntington’s disease. The hallmark of neuroinflammation is the glial activation, microglial activation [1].
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