Impaired KCC2 leads for neuranal network dysfunction and neurodevelopmental pathologies

Description

Abstract My research activity during last decade is dedicated to study the structure, function and physiological importance of KCC2, a neuron – restricted K+,Cl- co-transporter. KCC2 plays a critical role in setting neuronal i and control of the inhibitory strength of GABA and glycine neurotransmission. The dysfunction of KCC2 leads to i misbalance, change of the inhibitory action of GABA and formation of different types of epilepsies. A number of recent studies also assign an important role for modified i neuronal in etiology of multiple neurodevelopmental diseases (NDD), including autism spectrum disorders (ASDs), schizophrenia, Rett syndrome. However yet, none of studies have established a direct causal link between perturbed Cl- homeostasis and pathology. To better understand the role of Cl- in formation of NDD we are seeking for rare mutation in KCC2 associated with diseases and explore functional consequences of these mutation using different in-vitro and animal models. For example, we have found that mouse harboring functionally important mutations in KCC2 has modified neuronal i resulting in changes of neuronal circuits and associated with abnormal social behavior. Thus, KCC2 dysfunction itself can conduct to NDD. Respectively, upregulation of KCC2 constitutes an attractive therapeutic target.

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