2026-05-30T15:30:53Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/262862026-02-03T11:01:44Zcom_10630_2254col_10630_37953

Decreased medial prefrontal cortex activity related to impaired novel object preference task performance following GALR2 and Y1R agonists intranasal infusion Díaz-Sánchez, Estela López-Salas, Alexander Mirchandani-Duque, Marina Álvarez-Contino, José Erik Sánchez-Pérez, José Andrés Fuxe, Kjell Borroto Escuela, Dasiel Óscar García-Casares, Natalia Narváez-Peláez, Manuel Sistema nervioso-Degeneración-Tratamiento Enfermedades mentales- Quimioterapia Sistema nervioso-Enfermedades-Tratamiento Different brain regions’ interactions have been implicated in relevant neurological diseases, such as major depressive disorder (MDD), anxiety disorders, age-dependent cognitive decline, Alzheimer’s disease (AD) and addiction. We aim to explore the role of the medial prefrontal cortex (mPFC) in the Neuropeptide Y (NPY) and Galanin (GAL) interaction since we have demonstrated specific NPY and GAL interactions in brain areas related to these brain diseases. We performed GALR2 and Y1R agonists intranasal infusion and analyzed the mPFC activation through c-Fos expression. To assess the associated cellular mechanism we studied the formation of Y1R-GALR2 heteroreceptor complexes with in situ proximity ligation assay (PLA) and the expression of the brain- derived neurotrophic factor (BDNF). Moreover, the functional outcome of the NPY and GAL interaction on the mPFC was evaluated in the novel object preference task. We demonstrated that the intranasal administration of both agonists decrease the medial prefrontal cortex activation as shown with the c-Fos expression. These effects were mediated by the decreased formation of Y1R-GALR2 heteroreceptor complexes without affecting the BDNF expression. The functional outcome of this interaction was related to an impaired performance on the novel object preference task. Our data may suggest the translational development of new heterobivalent agonist pharmacophores acting on Y1R–GALR2 heterocomplexes in the medial prefrontal cortex for the novel therapy on neurodegenerative and psychiatric diseases. Data Sharing and Data Accessibility: The data that support the findings of this study are openly available in Institutional repository of the University of Malaga (RIUMA) and from the corresponding author upon reasonable request. 2023-04-19T09:02:29Z 2023-04-19T09:02:29Z 2023 journal article Díaz-Sánchez E, López-Salas A, Mirchandani-Duque M, Alvarez-Contino JE, Sánchez-Pérez JA, Fuxe K, Borroto-Escuela DO, García-Casares N, Narváez M. Decreased medial prefrontal cortex activity related to impaired novel object preference task performance following GALR2 and Y1R agonists intranasal infusion. Biomed Pharmacother. 2023 May;161:114433. doi: 10.1016/j.biopha.2023.114433. Epub 2023 Feb 26. PMID: 36848750. https://hdl.handle.net/10630/26286 https://doi.org/10.1016/j.biopha.2023.114433 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elsevier