Transcriptomic immaturity of the hippocampus and prefrontal cortex in patients with alcoholism

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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.

Original languageEnglish
Article number44531
JournalScientific reports
Volume7
DOIs
Publication statusPublished - 15-03-2017

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Prefrontal Cortex
Alcoholism
Hippocampus
Psychotic Disorders
Brain
Neurons
Dentate Gyrus
Alcoholics
Bipolar Disorder
Alcohol Drinking
Meta-Analysis
Epilepsy
Schizophrenia
Alcohols
Psychology
Gene Expression

All Science Journal Classification (ASJC) codes

  • General

Cite this

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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.",
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