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Effects of Immune Activation during Early or Late Gestation on N-Methyl-ᴅ-Aspartate Receptor Measures in Adult Rat Offspring

Citation

Rahman, T and Zavitsanou, K and Purves-Tyson, T and Harms, LR and Meehan, C and Schall, U and Todd, J and Hodgson, DM and Michie, PT and Weickert, CS, Effects of Immune Activation during Early or Late Gestation on N-Methyl-ᴅ-Aspartate Receptor Measures in Adult Rat Offspring, Frontiers in Psychiatry pp. 1-12. ISSN 1664-0640 (2017) [Refereed Article]


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Copyright Statement

ę 2017 Rahman, Zavitsanou, Purves-Tyson, Harms, Meehan, Schall, Todd, Hodgson, Michie and Weickert. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/

DOI: doi:10.3389/fpsyt.2017.00077

Abstract

Background: Glutamatergic receptor [N-methyl-ᴅ-aspartate receptor (NMDAR)] alterations within cortex, hippocampus, and striatum are linked to schizophrenia pathology. Maternal immune activation (MIA) is an environmental risk factor for the development of schizophrenia in offspring. In rodents, gestational timing of MIA may result in distinct behavioral outcomes in adulthood, but how timing of MIA may impact the nature and extent of NMDAR-related changes in brain is not known. We hypothesize that NMDARrelated molecular changes in rat cortex, striatum, and hippocampus are induced by MIA and are dependent on the timing of gestational inflammation and sex of the offspring.

Methods: Wistar dams were treated the with viral mimic, polyriboinosinic:polyribocytidylic acid (polyI:C), or vehicle on either gestational day 10 or 19. Fresh-frozen coronal brain sections were collected from offspring between postnatal day 63ľ91. Autoradiographic binding was used to infer levels of the NMDAR channel, and NR2A and NR2B subunits in cortex [cingulate (Cg), motor, auditory], hippocampus (dentate gyrus, cornu ammonis area 3, cornu ammonis area 1), and striatum [dorsal striatum, nucleus accumbens core, and nucleus accumbens shell (AS)]. NR1 and NR2A mRNA levels were measured by inásitu hybridization in cortex, hippocampus, and striatum in male offspring only.

Results: In the total sample, NMDAR channel binding was elevated in the Cg of polyI:C offspring. NR2A binding was elevated, while NR2B binding was unchanged, in all brain regions of polyI:C offspring overall. Male, but not female, polyI:C offspring exhibited increased NMDAR channel and NR2A binding in the striatum overall, and increased NR2A binding in the cortex overall. Male polyI:C offspring exhibited increased NR1 mRNA in the AS, and increased NR2A mRNA in cortex and subregions of the hippocampus.

Conclusion: MIA may alter glutamatergic signaling in cortical and hippocampal regions via alterations in NMDAR indices; however, this was independent of gestational timing. Male MIA offspring have exaggerated changes in NMDAR compared to females in both the cortex and striatum. The MIA-induced increase in NR2A may decrease brain plasticity and contribute to the exacerbated behavioral changes reported in males and indicate that the brains of male offspring are more susceptible to long-lasting changes in glutamate neurotransmission induced by developmental inflammation.

Item Details

Item Type:Refereed Article
Keywords:NMDA, Rat, poly I:C, Maternal immune activation, Glutamate, Hippocampus, Striatum
Research Division:Psychology and Cognitive Sciences
Research Group:Psychology
Research Field:Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Objective Division:Health
Objective Group:Public Health (excl. Specific Population Health)
Objective Field:Mental Health
UTAS Author:Meehan, C (Dr Crystal Meehan)
ID Code:126387
Year Published:2017
Web of Science® Times Cited:9
Deposited By:Psychology
Deposited On:2018-06-07
Last Modified:2018-07-23
Downloads:19 View Download Statistics

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