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Not Just a Bystander: The Emerging Role of Astrocytes and Research Tools in Studying Cognitive Dysfunctions in Schizophrenia
Authors:Chia-Yuan Chang  Da-Zhong Luo  Ju-Chun Pei  Ming-Che Kuo  Yi-Chen Hsieh  Wen-Sung Lai
Affiliation:1.Department of Psychology, National Taiwan University, Taipei 10617, Taiwan; (C.-Y.C.); (D.-Z.L.); (J.-C.P.); (Y.-C.H.);2.Neurobiology and Cognitive Science Center, National Taiwan University, Taipei 10617, Taiwan;3.Department of Neurology, National Taiwan University Hospital, Taipei 100225, Taiwan;4.Graduate Institute of Brain and Mind Sciences, National Taiwan University, Taipei 10617, Taiwan
Abstract:Cognitive dysfunction is one of the core symptoms in schizophrenia, and it is predictive of functional outcomes and therefore useful for treatment targets. Rather than improving cognitive deficits, currently available antipsychotics mainly focus on positive symptoms, targeting dopaminergic/serotoninergic neurons and receptors in the brain. Apart from investigating the neural mechanisms underlying schizophrenia, emerging evidence indicates the importance of glial cells in brain structure development and their involvement in cognitive functions. Although the etiopathology of astrocytes in schizophrenia remains unclear, accumulated evidence reveals that alterations in gene expression and astrocyte products have been reported in schizophrenic patients. To further investigate the role of astrocytes in schizophrenia, we highlighted recent progress in the investigation of the effect of astrocytes on abnormalities in glutamate transmission and impairments in the blood–brain barrier. Recent advances in animal models and behavioral methods were introduced to examine schizophrenia-related cognitive deficits and negative symptoms. We also highlighted several experimental tools that further elucidate the role of astrocytes. Instead of focusing on schizophrenia as a neuron-specific disorder, an additional astrocytic perspective provides novel and promising insight into its causal mechanisms and treatment. The involvement of astrocytes in the pathogenesis of schizophrenia and other brain disorders is worth further investigation.
Keywords:astrocytes, schizophrenia, cognitive dysfunction, glutamate transmission, glutamate trisynapse, blood–  brain barrier, animal models, behavioral tasks
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