Perinatal stress modulates glutamatergic functional connectivity: A post-synaptic density immediate early gene-based network analysis

Licia Vellucci; Giuseppe De Simone; Sara Morley-Fletcher; Elisabetta Filomena Buonaguro; Camilla Avagliano; Annarita Barone; Stefania Maccari; Felice Iasevoli; Andrea de Bartolomeis

doi:10.1016/j.pnpbp.2024.111032

Perinatal stress modulates glutamatergic functional connectivity: A post-synaptic density immediate early gene-based network analysis

Prog Neuropsychopharmacol Biol Psychiatry. 2024 May 16:133:111032. doi: 10.1016/j.pnpbp.2024.111032. Online ahead of print.

Authors

Licia Vellucci¹, Giuseppe De Simone², Sara Morley-Fletcher³, Elisabetta Filomena Buonaguro², Camilla Avagliano², Annarita Barone², Stefania Maccari⁴, Felice Iasevoli², Andrea de Bartolomeis⁵

Affiliations

¹ Section of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences and Dentistry, University Medical School of Naples "Federico II", Naples, Italy; Department of Translational Medical Sciences, University of Naples "Federico II", Via S. Pansini 5, 80131 Naples, Italy.
² Section of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences and Dentistry, University Medical School of Naples "Federico II", Naples, Italy.
³ Unité de Glycobiologie Structurale et Fonctionnelle, University of Lille, CNRS, UMR 8576, UGSF, F-59000 Lille, France; International Associated Laboratory (LIA) "Perinatal Stress and Neurodegenerative Diseases", Sapienza University of Rome - IRCCS, Neuromed, Rome, Italy and University of Lille - CNRS, UMR 8576, Lille, France.
⁴ Unité de Glycobiologie Structurale et Fonctionnelle, University of Lille, CNRS, UMR 8576, UGSF, F-59000 Lille, France; International Associated Laboratory (LIA) "Perinatal Stress and Neurodegenerative Diseases", Sapienza University of Rome - IRCCS, Neuromed, Rome, Italy and University of Lille - CNRS, UMR 8576, Lille, France; Department of Science and Medical-Surgical Biotechnology, Sapienza University of Rome, Rome, Italy.
⁵ Section of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences and Dentistry, University Medical School of Naples "Federico II", Naples, Italy. Electronic address: adebarto@unina.it.

PMID: 38762163
DOI: 10.1016/j.pnpbp.2024.111032

Abstract

Early life stress may induce synaptic changes within brain regions associated with behavioral disorders. Here, we investigated glutamatergic functional connectivity by a postsynaptic density immediate-early gene-based network analysis. Pregnant female Sprague-Dawley rats were randomly divided into two experimental groups: one exposed to stress sessions and the other serving as a stress-free control group. Homer1 expression was evaluated by in situ hybridization technique in eighty-eight brain regions of interest of male rat offspring. Differences between the perinatal stress exposed group (PRS) (n = 5) and the control group (CTR) (n = 5) were assessed by performing the Student's t-test via SPSS 28.0.1.0 with Bonferroni correction. Additionally, all possible pairwise Spearman's correlations were computed as well as correlation matrices and networks for each experimental group were generated via RStudio and Cytoscape. Perinatal stress exposure was associated with Homer1a reduction in several cortical, thalamic, and striatal regions. Furthermore, it was found to affect functional connectivity between: the lateral septal nucleus, the central medial thalamic nucleus, the anterior part of the paraventricular thalamic nucleus, and both retrosplenial granular b cortex and hippocampal regions; the orbitofrontal cortex, amygdaloid nuclei, and hippocampal regions; and lastly, among regions involved in limbic system. Finally, the PRS networks showed a significant reduction in multiple connections for the ventrolateral part of the anteroventral thalamic nucleus after perinatal stress exposure, as well as a decrease in the centrality of ventral anterior thalamic and amygdaloid nuclei suggestive of putative reduced cortical control over these regions. Within the present preclinical setting, perinatal stress exposure is a modifier of glutamatergic early gene-based functional connectivity in neuronal circuits involved in behaviors relevant to model neurodevelopmental disorders.

Keywords: Early life stress; Functional connectivity; Homer1a; Neurodevelopmental disorders; Post synaptic density.