The Poly I:C maternal immune stimulation model shows unique patterns of brain metabolism, morphometry, and plasticity in female rats.

Autor:	Casquero-Veiga M; Laboratorio de Imagen Médica, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.; Cardiovascular Imaging and Population Studies, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Lamanna-Rama N; Laboratorio de Imagen Médica, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.; Departamento de Bioingeniería e Ingeniería Aeroespacial, Escuela Técnica Superior de Ingeniería, Universidad Carlos III de Madrid, Madrid, Spain., Romero-Miguel D; Laboratorio de Imagen Médica, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.; Departamento de Bioingeniería e Ingeniería Aeroespacial, Escuela Técnica Superior de Ingeniería, Universidad Carlos III de Madrid, Madrid, Spain., Rojas-Marquez H; Laboratorio de Imagen Médica, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.; Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain.; Biocruces Bizkaia Health Research Institute, Barakaldo, Spain., Alcaide J; Neurobiology Unit, Cell Biology Departament, BIOTECMED Institute, Universitat de València, Burjassot, Spain.; CIBER de Salud Mental (CIBERSAM), Madrid, Spain.; Fundación Investigación Hospital Clínico de Valencia, INCLIVA, Valencia, Spain., Beltran M; Neurobiology Unit, Cell Biology Departament, BIOTECMED Institute, Universitat de València, Burjassot, Spain., Nacher J; Neurobiology Unit, Cell Biology Departament, BIOTECMED Institute, Universitat de València, Burjassot, Spain.; CIBER de Salud Mental (CIBERSAM), Madrid, Spain.; Fundación Investigación Hospital Clínico de Valencia, INCLIVA, Valencia, Spain., Desco M; Laboratorio de Imagen Médica, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.; CIBER de Salud Mental (CIBERSAM), Madrid, Spain.; Advanced Imaging Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.; Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Campus de Getafe, Madrid, Spain., Soto-Montenegro ML; Laboratorio de Imagen Médica, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.; CIBER de Salud Mental (CIBERSAM), Madrid, Spain.; High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut), University Rey Juan Carlos (URJC), Alcorcón, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in behavioral neuroscience [Front Behav Neurosci] 2023 Jan 06; Vol. 16, pp. 1022622. Date of Electronic Publication: 2023 Jan 06 (Print Publication: 2022).
DOI:	10.3389/fnbeh.2022.1022622
Abstrakt:	Introduction: Prenatal infections are associated with an increased risk of the onset of schizophrenia. Rodent models of maternal immune stimulation (MIS) have been extensively used in preclinical studies. However, many of these studies only include males, omitting pathophysiological features unique to females. The aim of this study is to characterize the MIS model in female rats using positron emission tomography (PET), structural magnetic resonance imaging (MR), and neuroplasticiy studies. Methods: In gestational day 15, Poly I:C (or Saline) was injected into pregnant Wistar rats to induce the MIS model. Imaging studies : [ 18 F]-fluoro-2-deoxy-D-glucose-PET scans of female-offspring were acquired at post-natal day (PND) 35 and PND100. Furthermore, T2-MR brain images were acquired in adulthood. Differences in FDG uptake and morphometry between groups were assessed with SPM12 and Regions of Interest (ROI) analyses. Ex vivo study : The density of parvalbumin expressing interneurons (PV), perineuronal nets (PNN), and parvalbumin expressing interneurons surrounded by perineuronal nets (PV-PNN) were evaluated in the prelimbic cortex and basolateral amygdala using confocal microscopy. ROIs and neuroplasticity data were analyzed by 2-sample T -test and 2-way-ANOVA analyses, respectively. Results: A significant increase in brain metabolism was found in all animals at adulthood compared to adolescence. MIS hardly modified brain glucose metabolism in females, highlighting a significant hypometabolism in the thalamus at adulthood. In addition, MIS induced gray matter (GM) enlargements in the pituitary, hippocampus, substantia nigra, and cingulate cortex, and GM shrinkages in some thalamic nuclei, cerebelar areas, and brainstem. Moreover, MIS induced white matter shrinkages in the cerebellum, brainstem and corpus callosum, along with cerebrospinal fluid enlargements in the lateral and 4th ventricles. Finally, MIS reduced the density of PV, PNN, and PV-PNN in the basolateral amygdala. Conclusion: Our work showed in vivo the differential pattern of functional and morphometric affectation in the MIS model in females, as well as the deficits caused at the synaptic level according to sex. The differences obtained highlight the relevance of including both sexes in psychiatric research in order to consider their pathophysiological particularities and successfully extend the benefits obtained to the entire patient population. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Casquero-Veiga, Lamanna-Rama, Romero-Miguel, Rojas-Marquez, Alcaide, Beltran, Nacher, Desco and Soto-Montenegro.)
Databáze:	MEDLINE
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