title: Transcriptomic immaturity of the hippocampus and prefrontal cortex in patients with alcoholism.
abstract: Alcoholism, which is defined as the recurring harmful use of alcohol despite its negative consequences, has a lifetime prevalence of 17.8%. Previous studies have shown that chronic alcohol consumption disrupts various brain functions and behaviours. However, the precise mechanisms that underlie alcoholism are currently unclear. Recently, we discovered "pseudo-immature" brain cell states of the dentate gyrus and prefrontal cortex (PFC) in mouse models of psychotic disorders and epileptic seizure. Similar pseudo-immaturity has been observed in patients with psychotic disorders, such as schizophrenia and bipolar disorder. Patients with alcoholism occasionally exhibit similar psychological symptoms, implying shared molecular and cellular mechanisms between these diseases. Here, we performed a meta-analysis to compare microarray data from the hippocampi/PFCs of the patients with alcoholism to data from these regions in developing human brains and mouse developmental data for specific cell types. We identified immature-like gene expression patterns in post-mortem hippocampi/PFCs of alcoholic patients and the dominant contributions of fast-spiking (FS) neurons to their pseudo-immaturity. These results suggested that FS neuron dysfunction and the subsequent imbalance between excitation and inhibition can be associated with pseudo-immaturity in alcoholism. These immaturities in the hippocampi/PFCs and the underlying mechanisms may explain the psychotic symptom generation and pathophysiology of alcoholism.
authors.affiliation: Department of Physiological Science, School of Life Science, The Graduate University for Advanced Studies, [SOKENDAI], Kanagawa, Japan.|Section of Behavior Patterns, Center for Genetic Analysis of Behaviour, National Institute for Physiological Sciences, Aichi, Japan.|Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Aichi, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Murano
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Aichi, Japan.
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Koshimizu
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Aichi, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Hagihara
authors.affiliation: Section of Behavior Patterns, Center for Genetic Analysis of Behaviour, National Institute for Physiological Sciences, Aichi, Japan.|Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Aichi, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001344:Autopsy; D019070:Cell Lineage / Q000235:genetics; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D046228:Microarray Analysis; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome / Q000235:genetics*