RT Journal Article
T1 Pyk2 in the amygdala modulates chronic stress sequelae via PSD-95-related microstructural changes
A1 Montalban, Enrica
A1 Al-Massadi Iglesias, Omar
A1 Sancho Balsells, Anna
A1 Brito, Verónica
A1 Pins, Benoit de
A1 Alberch, Jordi
A1 Ginés, Silvia
A1 Girault, Jean-Antoine
A1 Giralt, Albert
K1 Pyk2 protein
K1 Amygdala
K1 Stress
K1 Mice
K1 Major depressive disorder
AB Major depressive disorder (MDD) is a common disorder with a variety of symptoms including mood alterations,anhedonia, sleep and appetite disorders, and cognitive disturbances. Stressful life events are among the strongest riskfactors for developing MDD. At the cellular level, chronic stress results in the modification of dendritic spinemorphology and density. Here, we study the role of Pyk2 in the development of depressive-like symptoms induced bya model of chronic unpredictable mild stress (CUMS). Pyk2 is a non-receptor calcium-dependent protein-tyrosinekinase highly expressed in the forebrain principal neurons and involved in spine structure and density regulation. Weshow that Pyk2 knockout mice are less affected to anxiety-like and anhedonia-like phenotypes induced by the CUMSparadigm. Using region-specific knockout, we demonstrate that this phenotype is fully recapitulated by selective Pyk2inactivation in the amygdala. We also show that in the absence of Pyk2 the spine alterations, PSD-95 clustering, andNMDA receptors changes induced by the CUMS paradigm are prevented. Our results reveal a possible role for Pyk2 inthe response to stress and in synaptic markers expression and spine density regulation in the amygdala. We suggestthat Pyk2 contributes to stress-induced responses through micro-structural changes and that its deficit may contributeto the resilience to chronic stress
PB Nature Publishing Group
SN 2158-3188
YR 2019
FD 2019
LK http://hdl.handle.net/10347/22630
UL http://hdl.handle.net/10347/22630
LA eng
NO Montalban, E., Al-Massadi, O., Sancho-Balsells, A., Brito, V., Pins, B. d., Alberch, J., Ginés, S., Girault, J.A. and Giralt,A. (2019). Pyk2 in the amygdala modulates chronic stress sequelae via PSD-95-related micro-structural changes. Transl. Psychiatry 9, 3. doi: 10.1038/s41398-018-0352-y
NO A.G. is a Ramón y Cajal fellow (RYC-2016-19466). This work was supported by the NARSAD foundation (young investigator grant 2016 (Ref. 24803) to A.G.) and Ministerio de Ciencia e Innovació n (SAF2015-67474-R; MINECO/FEDER to S.G.). J.-A.G. lab was supported in part by Inserm, the Université Pierre et Marie Curie (UPMC, Sorbonne Université), the Fondation pour la Recherche Médicale, and the Bio-Psy (Biology for Psychiatry) laboratory of excellence. O.A.-M. was funded by the ISCIII/SERGAS thought a research contract “Sara Borrell” (CD14/ 00091). JA lab was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) (SAF-2014-57160R, SAF-2017-88076-R), Fundació Marató TV3 to J.A. and Instituto Carlos III: Centro de Investigación Biomédica en Red sobre enfermedades neurodegenerativas (CIBERNED), and RETICS RD12/ 0019/0002 to J.A.)
DS Minerva
RD 25 abr 2026