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Prog Neuropsychopharmacol Biol Psychiatry. 2019 Aug 9:109725. doi: 10.1016/j.pnpbp.2019.109725. [Epub ahead of print]

Glutamatergic postsynaptic density in early life stress programming: Topographic gene expression of mGlu5 receptors and Homer proteins.

Author information

1
Laboratory of Molecular and Translational Psychiatry, Unit of Treatment Resistant Psychosis, Section of Psychiatry and Psychology, Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, Naples, Italy.
2
Universiy of Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France; International Associated Laboratory (LIA), France/Italy "Prenatal Stress and Neurodegenerative Diseases", University of Lille - CNRS, UMR 8576, and Sapienza University of Rome, IRCCS Neuromed, Italy.
3
IRCCS Neuromed, 86077, Italy; Department of Human Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
4
Universiy of Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France; Department of Medico-Surgical Sciences and Biotechnology, Sapienza University of Rome, Rome, Italy. Electronic address: stefania.maccari@univ-lille1.fr.

Abstract

Type-5 metabotropic glutamate receptors (mGlu5) have been implicated in the mechanism of resilience to stress. They form part of the postsynaptic density (PSD), a thickening of the glutamatergic synapse that acts as a multimodal hub for multiple cellular signaling. Perinatal stress in rats triggers alterations that make adult offspring less resilient to stress. In the present study, we examined the expression of gene encoding the mGlu5 (Grm5), as well as those encoding the short and long isoforms of Homer proteins in different brain regions of the offspring of dams exposed to repeated episodes of restraint stress during pregnancy ("perinatally stressed" or PRS offspring). To this end, we investigated unconditioned behavioral response using the light/dark box test, as well as the expression of PSD genes (Homer1a, Homer1b, and Grm5), in the medial prefrontal cortex, cortex, caudate-putamen, amygdala, and dorsal hippocampus. PRS rats spent significantly less time in the light area than the control group. In the amygdala, Homer1a mRNA levels were significantly increased in PRS rats, whereas Homer1b and Grm5 mRNA levels were reduced. In contrast, the transcript encoding for Homer1a was significantly reduced in the medial prefrontal cortex, caudate-putamen, and dorsal hippocampus of PRS rats. We also evaluated the relative ratio between Homer1a and Homer1b/Grm5 expression, finding a significant shift toward the expression of Homer1a in the amygdala and toward Homer1b/Grm5 in the other brain regions. These topographic patterns of Homer1a, Homer1b, and mGlu5 gene expression were significantly correlated with risk-taking behavior measured in the light/dark box test. Remarkably, in the amygdala and in other brain regions, Homer1b and Grm5 expression showed positive correlation with time spent in the light box, whereas Homer1a in the amygdala showed a negative correlation with risk-taking behavior, in contrast with all other brain regions analyzed, wherein these correlations were positive. These results suggest that perinatal stress programs the developmental expression of PSD molecules involved in mGlu5 signaling in discrete brain regions, with a predominant role for the amygdala.

KEYWORDS:

Animal model; Early life programming; Gene expression; Stress; Synapse

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