@article{10902/30091,
year = {2023},
url = {https://hdl.handle.net/10902/30091},
abstract = {Cognitive impairment represents one of the core features of schizophrenia. Prolyl Oligopeptidase (POP) inhibition is an emerging strategy for compensating cognitive deficits in hypoglutamatergic states such as schizophrenia, although little is known about how POP inhibitors exert their pharmacological activity. The mitochondrial and nuclear protein Prohibitin 2 (PHB2) could be dysregulated in schizophrenia. However, altered PHB2 levels in schizophrenia linked to N-methyl-D-aspartate receptor (NMDAR) activity and cognitive deficits are still unknown. To shed light on this, we measured the PHB2 levels by immunoblot in a postmortem dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects, in the frontal pole of mice treated with the NMDAR antagonists phencyclidine and dizocilpine, and in rat cortical astrocytes and neurons treated with dizocilpine. Mice and cells were treated in combination with the POP inhibitor IPR19. The PHB2 levels were also analyzed by immunocytochemistry in rat neurons. The PHB2 levels increased in DLPFC in cases of chronic schizophrenia and were associated with cognitive impairments. NMDAR antagonists increased PHB2 levels in the frontal pole of mice and in rat astrocytes and neurons. High levels of PHB2 were found in the nucleus and cytoplasm of neurons upon NMDAR inhibition. IPR19 restored PHB2 levels in the acute NMDAR inhibition. These results show that IPR19 restores the upregulation of PHB2 in an acute NMDAR hypoactivity stage suggesting that the modulation of PHB2 could compensate NMDAR-dependent cognitive impairments in schizophrenia},
organization = {Funding: This research was funded by a Miguel Servet grant, MS16/00153-CP16/00153 to BR, financed and integrated into the National R+D+I and funded by the Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Health)—General Branch Evaluation and Promotion of Health Research— and the European Regional Development Fund (ERDF). This work was also supported by ISCIII PI18/00213 to BR, the Predoctoral Fellowship Program from the ISCIII (PFIS) FI19/00080 to E.V, FPU fellowship from the Spanish Ministry of Education, Culture, and Sports FPU17/06000 to E.E., the CONICYT-Doctorado Becas Chile 2015, 72160426 to AV, and the CIBERSAM (Spanish Ministry of Economy, Industry, and Competitiveness, Institute of Health Carlos III). CIBERSAM will be encharged to fund open access publication fees.},
publisher = {MDPI},
publisher = {International Journal of Molecular Sciences, 2023, 24, 6016},
title = {Inhibition of prolyl oligopeptidase restores prohibitin 2 levels in psychosis models: relationship to cognitive deficits in schizophrenia},
author = {Vila, Èlia and Pinacho, Raquel and Prades, Roger and Tarragó, Teresa and Castro Fernández, María Elena and Munarriz-Cuezva, Eva and Meana, J. Javier and Eugui-Anta, Ania and Roldan, Mònica and Vera-Montecinos, América and Ramos, Belén},
}