title: Synaptic dysfunction in schizophrenia.
abstract: Schizophrenia alters basic brain processes of perception, emotion, and judgment to cause hallucinations, delusions, thought disorder, and cognitive deficits. Unlike neurodegeneration diseases that have irreversible neuronal degeneration and death, schizophrenia lacks agreeable pathological hallmarks, which makes it one of the least understood psychiatric disorders. With identification of schizophrenia susceptibility genes, recent studies have begun to shed light on underlying pathological mechanisms. Schizophrenia is believed to result from problems during neural development that lead to improper function of synaptic transmission and plasticity, and in agreement, many of the susceptibility genes encode proteins critical for neural development. Some, however, are also expressed at high levels in adult brain. Here, we will review evidence for altered neurotransmission at glutamatergic, GABAergic, dopaminergic, and cholinergic synapses in schizophrenia and discuss roles of susceptibility genes in neural development as well as in synaptic plasticity and how their malfunction may contribute to pathogenic mechanisms of schizophrenia. We propose that mouse models with precise temporal and spatial control of mutation or overexpression would be useful to delineate schizophrenia pathogenic mechanisms.
authors.affiliation: Department of Neurology, Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, Augusta, GA 30912, USA.
authors.forename: Dong-Min
authors.initials: DM
authors.lastname: Yin
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Chen
authors.forename: Anupama
authors.initials: A
authors.lastname: Sathyamurthy
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease / Q000196:embryology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009473:Neuronal Plasticity; D011950:Receptors, Cholinergic / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine; D004298:Dopamine