Chronic Alcohol Use Induces Molecular Genetic Changes in the Dorsomedial Thalamus of People with Alcohol-Related Disorders

Hade, Andreas-Christian, Philips, Mari-Anne, Reimann, Ene, Jagomae, Toomas, Eskla, Kattri-Liis, Traks, Tanel, Prans, Ele, Koks, Sulev ORCID: 0000-0001-6087-6643, Vasar, Eero and Vali, Marika (2021) Chronic Alcohol Use Induces Molecular Genetic Changes in the Dorsomedial Thalamus of People with Alcohol-Related Disorders. BRAIN SCIENCES, 11 (4). 435-.

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Official URL: http://dx.doi.org/10.3390/brainsci11040435

Abstract

The Mediodorsal (MD) thalamus that represents a fundamental subcortical relay has been underrepresented in the studies focusing on the molecular changes in the brains of subjects with alcohol use disorder (AUD). In the current study, MD thalamic regions from AUD subjects and controls were analyzed with Affymetrix Clariom S human microarray. Long-term alcohol use induced a significant (FDR ≤ 0.05) upregulation of 2802 transcripts and downregulation of 1893 genes in the MD thalamus of AUD subjects. A significant upregulation of GRIN1 (glutamate receptor NMDA type 1) and FTO (alpha-ketoglutarate dependent dioxygenase) was confirmed in western blot analysis. Immunohistochemical staining revealed similar heterogenous distribution of GRIN1 in the thalamic nuclei of both AUD and control subjects. The most prevalent functional categories of upregulated genes were related to glutamatergic and GABAergic neurotransmission, cellular metabolism, and neurodevelopment. The prevalent gene cluster among down-regulated genes was immune system mediators. Forty-two differentially expressed genes, including FTO, ADH1B, DRD2, CADM2, TCF4, GCKR, DPP6, MAPT and CHRH1, have been shown to have strong associations (FDR <i>p</i> < 10<sup>-8</sup>) with AUD or/and alcohol use phenotypes in recent GWA studies. Despite a small number of subjects, we were able to detect robust molecular changes in the mediodorsal thalamus caused by alcohol emphasizing the importance of deeper brain structures such as diencephalon, in the development of AUD-related dysregulation of neurocircuitry.

Item Type:	Article
Uncontrolled Keywords:	alcoholism, alcohol use disorder, autopsy, mediodorsal thalamus, GRIN1, FTO
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	07 Jul 2021 10:17
Last Modified:	13 Feb 2024 17:17
DOI:	10.3390/brainsci11040435
Open Access URL:	https://doi.org/10.3390/brainsci11040435
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3129127