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Single Neuron and Microglia Gene Expression Networks Demonstrate Cellular Subphenotype Shifts and Altered Glial‐Neuronal Signaling in Solitary Nucleus during Alcohol Withdrawal: A Time Series
Author(s) -
O'Sullivan Sean J,
Park James,
McintoshClark Damani,
Schwaber James S
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.641.5
Subject(s) - amygdala , central nucleus of the amygdala , neuroscience , extended amygdala , alcohol dependence , microglia , drug withdrawal , addiction , nucleus accumbens , receptor , nucleus , medicine , psychology , biology , inflammation , alcohol , psychiatry , stria terminalis , drug , biochemistry
Alcohol use disorder remains a major societal and healthcare challenge motivating investigation into novel mechanisms of alcohol addiction. Negative‐reinforcement models of addiction postulate that avoidance of negative physical and emotional symptoms during withdrawal drive drug‐seeking. Alcohol withdrawal syndrome is characterized by autonomic dysregulation and negative emotion implicating the strongly connected amygdala and solitary nucleus (NTS) involved in autonomic inputs, outputs, and emotional states in the pathophysiology of alcohol withdrawal. Our previous work demonstrates a neuroinflammatory state in the amygdala during alcohol withdrawal, which we speculate contributes to the negative physical and emotional withdrawal symptoms and consequently drug‐seeking. Here, we investigated the effect of alcohol withdrawal on gene expression in single glucagon‐like peptide 1 (GLP‐1) neurons, adrenergic neurons, and microglia in the NTS. GLP‐1 neurons in this region receive autonomic inputs via vagal afferents and signal to amygdala neurons co‐expressing GLP‐1 receptors and corticotropin‐releasing factor. NTS adrenergic neurons respond to higher‐order inputs to maintain cardiovascular homeostasis. Control, ethanol‐dependent, and rats undergoing ethanol withdrawal at 8, 32, and 176 hour time points were sampled. Single cells were harvested using using laser‐capture microdissection, and microfluidic RT‐qPCR was employed to generate a high‐dimensional dataset. Cellular subphenotypes were characterized and local glial‐neuronal signaling networks were described based on gene networks that defined these subphenotypes. We found an increase in inflammatory subphentoypes in the 8 and 32 hour withdrawal condition with the 176 hour withdrawal condition demonstrating decreased GABA receptor expression. Preproglucagon (Gcg), the GLP‐1 precursor transcript, was found to be upregulated only in alcohol withdrawal conditions. The levels of this transcript opposed levels of the norepinephrine precursor tyrosine hydroxylase transcript suggesting these two signaling ligands have oppositional regulation in alcohol withdrawal. Support or Funding Information U01HL133360‐01 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .