C1q deletion exacerbates stress-induced learned helplessness behavior and induces neuroinflammation in mice

Abstract Increased levels of pro-inflammatory cytokines have been reported in postmortem brain samples and in the blood of depressed subjects. However, the inflammatory pathways that lead to depressive-like symptoms are not well understood. Using the learned helplessness (LH) model of depression, we...

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Main Authors: Amit Kumar Madeshiya, Carl Whitehead, Ashutosh Tripathi, Anilkumar Pillai
Format: Article
Language:English
Published: Nature Publishing Group 2022-02-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-022-01794-4
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author Amit Kumar Madeshiya
Carl Whitehead
Ashutosh Tripathi
Anilkumar Pillai
author_facet Amit Kumar Madeshiya
Carl Whitehead
Ashutosh Tripathi
Anilkumar Pillai
author_sort Amit Kumar Madeshiya
collection DOAJ
description Abstract Increased levels of pro-inflammatory cytokines have been reported in postmortem brain samples and in the blood of depressed subjects. However, the inflammatory pathways that lead to depressive-like symptoms are not well understood. Using the learned helplessness (LH) model of depression, we examined the role of C1q, the initiator of classical complement pathway in mediating stress-induced depressive-like behavior in mice. We observed no significant changes in social behavior, despair behavior, spatial memory, and aggressive behavior between the wild type (WT) and C1q knockout (KO) mice. However, C1q deletion exacerbated the inescapable electric foot shock-induced learned helplessness behavior in mice. We found significant reductions in C1q mRNA levels in the prefrontal cortex (PFC) of WT helpless mice as compared to the naïve mice. Increased levels of pro-inflammatory cytokines were found in the PFC of C1q KO mice. These findings suggest that classical complement pathway-mediated learned helplessness behavior is accompanied by neuroinflammatory changes under stressful conditions.
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spelling doaj.art-bd6c6639dca646d1ab90a134ea9351092022-12-22T01:34:10ZengNature Publishing GroupTranslational Psychiatry2158-31882022-02-011211810.1038/s41398-022-01794-4C1q deletion exacerbates stress-induced learned helplessness behavior and induces neuroinflammation in miceAmit Kumar Madeshiya0Carl Whitehead1Ashutosh Tripathi2Anilkumar Pillai3Pathophysiology of Neuropsychiatric Disorders Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth)Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta UniversityPathophysiology of Neuropsychiatric Disorders Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth)Pathophysiology of Neuropsychiatric Disorders Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth)Abstract Increased levels of pro-inflammatory cytokines have been reported in postmortem brain samples and in the blood of depressed subjects. However, the inflammatory pathways that lead to depressive-like symptoms are not well understood. Using the learned helplessness (LH) model of depression, we examined the role of C1q, the initiator of classical complement pathway in mediating stress-induced depressive-like behavior in mice. We observed no significant changes in social behavior, despair behavior, spatial memory, and aggressive behavior between the wild type (WT) and C1q knockout (KO) mice. However, C1q deletion exacerbated the inescapable electric foot shock-induced learned helplessness behavior in mice. We found significant reductions in C1q mRNA levels in the prefrontal cortex (PFC) of WT helpless mice as compared to the naïve mice. Increased levels of pro-inflammatory cytokines were found in the PFC of C1q KO mice. These findings suggest that classical complement pathway-mediated learned helplessness behavior is accompanied by neuroinflammatory changes under stressful conditions.https://doi.org/10.1038/s41398-022-01794-4
spellingShingle Amit Kumar Madeshiya
Carl Whitehead
Ashutosh Tripathi
Anilkumar Pillai
C1q deletion exacerbates stress-induced learned helplessness behavior and induces neuroinflammation in mice
Translational Psychiatry
title C1q deletion exacerbates stress-induced learned helplessness behavior and induces neuroinflammation in mice
title_full C1q deletion exacerbates stress-induced learned helplessness behavior and induces neuroinflammation in mice
title_fullStr C1q deletion exacerbates stress-induced learned helplessness behavior and induces neuroinflammation in mice
title_full_unstemmed C1q deletion exacerbates stress-induced learned helplessness behavior and induces neuroinflammation in mice
title_short C1q deletion exacerbates stress-induced learned helplessness behavior and induces neuroinflammation in mice
title_sort c1q deletion exacerbates stress induced learned helplessness behavior and induces neuroinflammation in mice
url https://doi.org/10.1038/s41398-022-01794-4
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