神经元开关控制小胶质细胞.pdfVIP

Review TRENDS in Neurosciences Vol.30 No.11 Neuronal ‘On’ and ‘Off’ signals control microglia 1 2 3 1 Knut Biber , Harald Neumann , Kazuhide Inoue and Hendrikus W.G.M. Boddeke 1 Department of Medical Physiology, University Medical Center Groningen (UMCG), University of Groningen, Groningen, 9713AV, The Netherlands 2 Institute of Reconstructive Neurobiology, LIFE BRAIN Center, University of Bonn, 53127 Bonn, Germany 3 Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 812-8582, Japan Recent findings indicate that neurons are not merely (IL)-4 induced a neuroprotective phenotype [10], which passive targets of microglia but rather control microglial corroborates many earlier in vitro findings that concern activity. The variety of different signals that neurons use neuroprotective microglia activity (for a review, see [1,2]). to control microglia can be divided into two categories: Also, numerous neuroprotective effects of activated micro- ‘Off’ signals constitutively keep microglia in their resting glia have been demonstrated recently in vivo. Microglia are state and antagonize proinflammatory activity. ‘On’ sig- beneficial in a model of nitric oxide (NO)-dependent exci- nals are inducible and include purines, chemokines, totoxicity [11] and in animal models of stroke [12], as well glutamate. They instruct microglia activation under as in mouse models of amyotrophic lateral sclerosis (ALS) pathological conditions towards a beneficial or detri- [13] and of Alzheimer’s disease [14]. mental phenotype. Various