RT Journal Article
T1 Chronic mild stress dysregulates autophagy, membrane dynamics, and lysosomal status in frontal cortex and hippocampus of rats
A1 Ulecia Morón, Cristina
A1 González Bris, Álvaro
A1 Mac-Dowell Mata, Karina Soledad
A1 Cerveró-García, Pilar
A1 Muñoz Madrigal, José Luis
A1 García Bueno, Borja
A1 Pérez Pereira, Marta
A1 Leza Cerro, Juan Carlos
A1 Caso Fernández, Javier Rubén
AB 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.
PB Elsevier
SN 0924-977X
YR 2025
FD 2025-03-07
LK https://hdl.handle.net/20.500.14352/125812
UL https://hdl.handle.net/20.500.14352/125812
LA eng
NO Ulecia-Morón, C., Bris, Á. G., MacDowell, K. S., Cerveró-García, P., Madrigal, J. L. M., García-Bueno, B., Pereira, M. P., Leza, J. C., & Caso, J. R. (2025). Chronic mild stress dysregulates autophagy, membrane dynamics, and lysosomal status in frontal cortex and hippocampus of rats. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 94, 24–35. https://doi.org/10.1016/j.euroneuro.2025.02.005
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Agencia Estatal de Investigación
NO Unión Europea
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 20 ene 2026