Protective effects of nicergoline against neuronal cell death induced by activated microglia and astrocytes.
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.
Mizuno
Tetsuya
T
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8601, Japan. tmizuno@riem.nagoya-u.ac.jp
Kuno
Reiko
R
Nitta
Atsumi
A
Nabeshima
Toshitaka
T
Zhang
Guiqin
G
Kawanokuchi
Jun
J
Wang
Jinyan
J
Jin
Shijie
S
Takeuchi
Hideyuki
H
Suzumura
Akio
A
D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D009530:Nicergoline / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D009414:Nerve Growth Factors; D018697:Nootropic Agents; D013481:Superoxides; D009530:Nicergoline