Chronic mild stress dysregulates autophagy, membrane dynamics, and lysosomal status in frontal cortex and hippocampus of rats

IF 6.1 2区 医学 Q1 CLINICAL NEUROLOGY
Cristina Ulecia-Morón , Álvaro G. Bris , Karina S. MacDowell , Pilar Cerveró-García , José L.M. Madrigal , Borja García-Bueno , Marta P. Pereira , Juan C. Leza , Javier R. Caso
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引用次数: 0

Abstract

Inflammation has been related to major depressive disorder pathophysiology. Autophagy, a degradative pathway regulating inflammation and immunity, has emerged as a potential contributor. Among others, we characterized, in frontal cortex (FC) and hippocampus (Hp), autophagy markers (upregulations in mTOR, ATG7, and ATG 16L1, and downregulations in ULK1, BECLIN1, phospho-SQSTM1, ATG3, ATG12, and ATG 16L1), effectors of the endosomal sorting complexes required for transport (overexpression in HRS, VPS37A, CHMP6, and GALECTIN 3, and downregulations in STAM2, TSG101, VPS28, VPS37A, CHMP5, VPS4B, and GALECTIN 9), and lysosomal proteins (LAMP1, LAMP2A, MANNOSE RECEPTOR, HSC70, HSP70, CATHEPSIN D and B, and CYSTATIN C, whose variations are dependent on lysosomal nature and brain region) of male rats exposed to chronic mild stress, a model of depression, compared to control rats. Results indicate that chronic stress alters protein expression of autophagy and the endosomal sorting complexes required for transport markers in a region-specific manner, plus increases lysosomal presence, oppositely modulating lysosomal proteins in each structure. Additionally, astrocytes seemed to exert an essential role in the regulation of the autophagy adaptor SQSTM1/p62. In conclusion, stress-induced protein disruptions in these pathways highlight their differential modulation after chronic stress exposure and their potential role in maintaining brain homeostasis during the stress response, making them promising targets for new therapeutic strategies in stress-related pathologies.
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来源期刊
European Neuropsychopharmacology
European Neuropsychopharmacology 医学-精神病学
CiteScore
10.30
自引率
5.40%
发文量
730
审稿时长
41 days
期刊介绍: European Neuropsychopharmacology is the official publication of the European College of Neuropsychopharmacology (ECNP). In accordance with the mission of the College, the journal focuses on clinical and basic science contributions that advance our understanding of brain function and human behaviour and enable translation into improved treatments and enhanced public health impact in psychiatry. Recent years have been characterized by exciting advances in basic knowledge and available experimental techniques in neuroscience and genomics. However, clinical translation of these findings has not been as rapid. The journal aims to narrow this gap by promoting findings that are expected to have a major impact on both our understanding of the biological bases of mental disorders and the development and improvement of treatments, ideally paving the way for prevention and recovery.
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