Interaction of maternal immune activation and genetic interneuronal inhibition

Allison Anderson, Thiago C. Genaro-Mattos, Luke B. Allen, Katalin Koczok, Zeljka Korade, Karoly Mirnics

Research output: Contribution to journalArticlepeer-review

Abstract

Genes and environment interact during intrauterine life, and potentially alter the developmental trajectory of the brain. This can result in life-long consequences on brain function. We have previously developed two transgenic mouse lines that suppress Gad1 expression in parvalbumin (PVALB) and neuropeptide Y (NPY) expressing interneuron populations using a bacterial artificial chromosome (BAC)-driven miRNA-based silencing technology. We were interested to assess if maternal immune activation (MIA), genetic interneuronal inhibition, and the combination of these two factors disrupt and result in long-term changes in neuroinflammatory gene expression, sterol biosynthesis, and acylcarnitine levels in the brain of maternally exposed offspring. Pregnant female WT mice were given a single intraperitoneal injection of saline or polyinosinic–polycytidilic acid [poly(I:C)] at E12.5. Brains of offspring were analyzed at postnatal day 90. We identified complex and persistent neuroinflammatory gene expression changes in the hippocampi of MIA-exposed offspring, as well in the hippocampi of Npy/Gad1 and Pvalb/Gad1 mice. In addition, both MIA and genetic inhibition altered the post-lanosterol sterol biosynthesis in the neocortex and disrupted the typical acylcarnitine profile. In conclusion, our findings suggest that both MIA and inhibition of interneuronal function have long-term consequences on critical homeostatic mechanisms of the brain, including immune function, sterol levels, and energy metabolism.

Original languageEnglish (US)
Article number147370
JournalBrain Research
Volume1759
DOIs
StatePublished - May 15 2021

Keywords

  • Acylcarnitines
  • Interneuron
  • Maternal immune activation
  • Neuroinflammation
  • Schizophrenia
  • Sterol profile

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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