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Neuropharmacology. 2019 Mar 1;146:264-275. doi: 10.1016/j.neuropharm.2018.12.007. Epub 2018 Dec 8.

Microglia in the developing prefrontal cortex of rats show dynamic changes following neonatal disconnection of the ventral hippocampus.

Author information

1
Axe neurosciences, Centre de recherche du CHU de Québec, Université Laval, Québec, Québec, Canada.
2
Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, Québec, Canada.
3
Axe neurosciences, Centre de recherche du CHU de Québec, Université Laval, Québec, Québec, Canada. Electronic address: tremblay.marie-eve@crchudequebec.ulaval.ca.
4
Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, Québec, Canada. Electronic address: lalit.srivastava@mcgill.ca.

Abstract

Impaired ventral hippocampal (VH)-prefrontal cortex (PFC) connectivity is implicated in many cognitive and behavioral disorders. Excitotoxic neonatal VH (nVH) lesion in rat pups has been shown to induce synaptic pruning in the PFC as well as behavioral changes of relevance to developmental neuropsychiatric disorders. In the current study, we hypothesized that microglia, immune cells required for proper brain development and plasticity, may play a role in the development of abnormal behaviors in the nVH-lesioned animals. Ibotenic acid-induced nVH lesion was induced in postnatal day (P)7 male rats. Developmental changes in microglial density, morphology, ultrastructure and gene expression were analyzed in the PFC at P20 and P60. Our results revealed increased microglial reactivity and phagocytic activity in the lesioned rats at P20. Increased mRNA levels of C3 and C1q, complement molecules involved in synaptic pruning, were concomitantly observed. Diminished, but maintained, microglial reactivity and reduced antioxidative defenses were identified in lesioned rats at P60. Behavioral deficits were significantly reduced in the post-pubertal rats by suppressing microglial reactivity by a one-week minocycline treatment immediately after the lesion, These results suggest that early-life disconnection of the VH has long-lasting consequences for microglial functions in the connected structures. Alterations in microglia may underlie synaptic reorganization and behavioral deficits observed following neonatal VH disconnection.

KEYWORDS:

Animal model; Microglia; Neurodevelopment; Prefrontal cortex; Schizophrenia

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