RT Journal Article
T1 Decreased medial prefrontal cortex activity related to impaired novel object  preference task performance following GALR2 and Y1R agonists  intranasal infusion
A1 Díaz-Sánchez, Estela
A1 López-Salas, Alexander
A1 Mirchandani-Duque, Marina
A1 Álvarez-Contino, José Erik
A1 Sánchez-Pérez, José Andrés
A1 Fuxe, Kjell
A1 Borroto Escuela, Dasiel Óscar
A1 García-Casares, Natalia
A1 Narváez-Peláez, Manuel
K1 Sistema nervioso-Degeneración-Tratamiento
K1 Enfermedades mentales- Quimioterapia
K1 Sistema nervioso-Enfermedades-Tratamiento
AB Different brain regions’ interactions have been implicated in relevant neurological diseases, such as majordepressive disorder (MDD), anxiety disorders, age-dependent cognitive decline, Alzheimer’s disease (AD) andaddiction. We aim to explore the role of the medial prefrontal cortex (mPFC) in the Neuropeptide Y (NPY) andGalanin (GAL) interaction since we have demonstrated specific NPY and GAL interactions in brain areas relatedto these brain diseases. We performed GALR2 and Y1R agonists intranasal infusion and analyzed the mPFCactivation through c-Fos expression. To assess the associated cellular mechanism we studied the formation ofY1R-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 themPFC was evaluated in the novel object preference task. We demonstrated that the intranasal administration ofboth agonists decrease the medial prefrontal cortex activation as shown with the c-Fos expression. These effectswere mediated by the decreased formation of Y1R-GALR2 heteroreceptor complexes without affecting the BDNFexpression. The functional outcome of this interaction was related to an impaired performance on the novelobject preference task. Our data may suggest the translational development of new heterobivalent agonistpharmacophores acting on Y1R–GALR2 heterocomplexes in the medial prefrontal cortex for the novel therapy onneurodegenerative and psychiatric diseases.Data Sharing and Data Accessibility: The data that support the findings of this study are openly available inInstitutional repository of the University of Malaga (RIUMA) and from the corresponding author upon reasonablerequest.
PB Elsevier
YR 2023
FD 2023
LK https://hdl.handle.net/10630/26286
UL https://hdl.handle.net/10630/26286
LA eng
NO 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.
NO Partial funding for open access charge: Universidad de Málaga / CBUAThis research was funded by the UMA18-FEDERJA-100 and ProyExcel_00613 (Junta de Andalucía, Spain), Proyecto Jovenes Inves-tigadores (B1–2019-04), Proyecto puente (B4–2021-06) (Universidad de M álaga, Spain), to MN. Partial funding for open access charge: Universidad de Málaga/CBUA. Swedish Medical Research Council (Sweden) (62X-00715–50-3), to KF, by Stiftelsen Olle Engkvist Byggmästare (Sweden) to KF.Hj ̈arnfonden (Sweden) (F02018–0286), (F02019–0296), Karolinska Institutet Forskningsstiftelser (Sweden), and EMERGIA (2020,39318) to D.O.B.-E. D.O.B.-E. belongs to the “Academia de Biólogos Cubanos” group, Cuba.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 26 ene 2026