Dallérac Glenn, Rouach Nathalie
Neuroglial Interactions in Cerebral Physiopathology, Center for Interdisciplinary Research in Biology, Collège de France, Centre National de la Recherche Scientifique UMR 7241, Institut National de la Santé et de la Recherche Médicale U1050, Labex Memolife, PSL Research University, Paris, France.
Prog Neurobiol. 2016 Sep;144:48-67. doi: 10.1016/j.pneurobio.2016.01.003. Epub 2016 Mar 8.
Astrocytes are now viewed as key elements of brain wiring as well as neuronal communication. Indeed, they not only bridge the gap between metabolic supplies by blood vessels and neurons, but also allow fine control of neurotransmission by providing appropriate signaling molecules and insulation through a tight enwrapping of synapses. Recognition that astroglia is essential to neuronal communication is nevertheless fairly recent and the large body of evidence dissecting such role has focused on the synaptic level by identifying neuro- and gliotransmitters uptaken and released at synaptic or extrasynaptic sites. Yet, more integrated research deciphering the impact of astroglial functions on neuronal network activity have led to the reasonable assumption that the role of astrocytes in supervising synaptic activity translates in influencing neuronal processing and cognitive functions. Several investigations using recent genetic tools now support this notion by showing that inactivating or boosting astroglial function directly affects cognitive abilities. Accordingly, brain diseases resulting in impaired cognitive functions have seen their physiopathological mechanisms revisited in light of this primary protagonist of brain processing. We here provide a review of the current knowledge on the role of astrocytes in cognition and in several brain diseases including neurodegenerative disorders, psychiatric illnesses, as well as other conditions such as epilepsy. Potential astroglial therapeutic targets are also discussed.
如今,星形胶质细胞被视为大脑布线以及神经元通讯的关键要素。事实上,它们不仅在血管与神经元之间的代谢供应方面起到桥梁作用,还通过提供适当的信号分子以及紧密包裹突触来实现绝缘,从而对神经传递进行精细控制。然而,认识到星形胶质细胞对神经元通讯至关重要却是相当近期的事情,并且大量剖析这种作用的证据通过识别在突触或突触外位点摄取和释放的神经递质和胶质递质,聚焦于突触层面。然而,更多综合研究解读星形胶质细胞功能对神经网络活动的影响,合理推测出星形胶质细胞在监督突触活动方面的作用转化为对神经元加工和认知功能的影响。现在,几项使用最新基因工具的研究通过表明使星形胶质细胞功能失活或增强直接影响认知能力,支持了这一观点。因此,鉴于大脑加工过程中的这一主要角色,导致认知功能受损的脑部疾病的生理病理机制已被重新审视。我们在此综述了关于星形胶质细胞在认知以及包括神经退行性疾病、精神疾病以及癫痫等其他病症在内的几种脑部疾病中作用的当前知识。还讨论了潜在的星形胶质细胞治疗靶点。