Protective effects of nicergoline against neuronal cell death induced by activated microglia and astrocytes.

Tetsuya Mizuno, Reiko Kuno, Atsumi Nitta, Toshitaka Nabeshima, Guiqin Zhang, Jun Kawanokuchi, Jinyan Wang, Shijie Jin, Hideyuki Takeuchi, Akio Suzumura

Index: Brain Res. 1066(1-2) , 78-85, (2005)

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Abstract

We examined the neuroprotective role of nicergoline in neuron-microglia or neuron-astrocytes co-cultures. Nicergoline, an ergoline derivative, significantly suppressed the neuronal cell death induced by co-culture with activated microglia or astrocytes stimulated with lipopolysaccharide (LPS) and interferon (IFN)-gamma. To elucidate the mechanism by which nicergoline exerts a neuroprotective effect, we examined the production of inflammatory mediators and neurotrophic factors in activated microglia and astrocytes following nicergoline treatment. In microglia stimulated with LPS and IFN-gamma, nicergoline suppressed the production of superoxide anions, interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha in a dose-dependent manner. In astrocytes, nicergoline also suppressed the production of proinflammatory cytokines and enhanced brain-derived neurotrophic factor (BDNF). Thus, nicergoline-mediated neuroprotection resulted primarily from the inhibition of inflammatory mediators and the upregulation of neurotrophic factors by glial cells.