Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype

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  • dc.contributor.author Miquel-Rio, Lluis
  • dc.contributor.author Jericó-Escolar, Judith
  • dc.contributor.author Sarriés-Serrano, Unai
  • dc.contributor.author Yanes-Castilla, Claudia
  • dc.contributor.author Torres-López, María
  • dc.contributor.author Argibay, Uxia
  • dc.contributor.author Paz, Verónica
  • dc.contributor.author Casal, Carmen
  • dc.contributor.author Muñoz-Moreno, Emma
  • dc.contributor.author López-Gil, Xavier
  • dc.contributor.author Bortolozzi, Analía
  • dc.date.accessioned 2025-11-24T07:02:03Z
  • dc.date.available 2025-11-24T07:02:03Z
  • dc.date.issued 2025
  • dc.description.abstract Anxiety and depression are common in Parkinson’s disease (PD), affecting quality of life. Aggregates of α-synuclein (α-Syn) are found in serotonergic (5-HT) raphe nuclei early in the disease, but their relationship to brain changes is unclear. We investigated synaptic plasticity, neuronal activity, and functional magnetic resonance imaging (fMRI)-based brain connectivity in a PD-like mouse model with depressive phenotype. AAV-induced human α-Syn accumulation in raphe 5-HT neurons causes progressive synaptic pathology in interconnected brain regions. This is marked by lower MAP-2, PSD95 and higher SV2A, VAMP2, which are key to synaptic structure and function, as confirmed in human brain tissue samples. Abnormalities in Egr-1-dependent neuronal activity and region-specific differences in resting-state functional brain activity were also detected eight weeks post-AAV infusion, before neurodegeneration. This provides evidence for synaptic and fMRI markers associated with α-Syn pathology in emotional brain circuits, and has translational importance for identifying PD patients at risk for depression.en
  • dc.description.sponsorship This work was supported by MCIU/AEI/FEDER, UE grant (PID2019-105136RB-100, PID2022-141700OB-I00, MCIN/AEI/10.13039/501100011033 to A.B.), and AGAUR 2021-SGR-01358, Catalan Government. CB/07/09/0034 Center for Networked Biomedical Research on Mental Health (CIBERSAM). We also thank the Spanish Stress Research Network, MCIN/AEI/10.13039/501100011033. U.S.S. is a recipient of a fellowship from the Non- Doctor Researcher Formation Pre-doctoral Program of Basque Government, Spain. U.A. is a recipient of a fellowship from the State Research Agency for the training of predoctoral research personnel (PREP2022-000676) associated to a generation of knowledge project (PID2022-141700OB-I00). The authors would like to thank the staff members of the Biobank of the Clinic Hospital Barcelona - IDIBAPS for their collaboration in the study.en
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Miquel-Rio L, Jericó-Escolar J, Sarriés-Serrano U, Yanes-Castilla C, Torres-López M, Argibay U, et al. Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype. NPJ Parkinsons Dis. 2025;11(1):242. DOI: 10.1038/s41531-025-01073-1
  • dc.identifier.doi http://dx.doi.org/10.1038/s41531-025-01073-1
  • dc.identifier.issn 2373-8057
  • dc.identifier.uri http://hdl.handle.net/10230/71970
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof NPJ Parkinsons Disease. 2025;11(1):242
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-105136RB-100
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-141700OB-I00
  • dc.rights This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.other Malaltiesca
  • dc.subject.other Neurociènciesca
  • dc.subject.other Biologia molecularca
  • dc.title Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotypeen
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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