Using a maternal immune stimulation model of schizophrenia to study behavioral and neurobiological alterations over the developmental course

Ravit Hadar, M. Luisa Soto-Montenegro, Thomas Götz, Franziska Wieske, Reinhard Sohr, Manuel Desco, Clement Hamani, Ina Weiner, Javier Pascau, Christine Winter

Research output: Contribution to journalArticlepeer-review

Abstract

A growing body of evidence sheds light on the neurodevelopmental nature of schizophrenia with symptoms typically emerging during late adolescence or young adulthood. We compared the pre-symptomatic adolescence period with the full symptomatic period of adulthood at the behavioral and neurobiological level in the poly I:C maternal immune stimulation (MIS) rat model of schizophrenia. We found that in MIS-rats impaired sensorimotor gating, as reflected in disrupted prepusle inhibition (PPI), emerged post-pubertally, with behavioral deficits being only recorded in adulthood but not during adolescence. Using post mortem HPLC we found that MIS-rats show distinct dopamine and serotonin changes in the medial prefrontal cortex (mPFC), nucleus accumbens (Nacc), caudate putamen, globus pallidus, and hippocampus. Further, FDG-PET has shown that these animals had lower glucose uptake in the ventral hippocampus and PFC and a higher metabolism in the amygdala and Nacc when compared to controls. Changes in neurotransmission and metabolic activity varied across brain structures with respect to first appearance and further development. In the mPFC and Hipp, MIS-rats showed abnormal neurochemical and metabolic activity prior to and with the development of behavioral deficits in both adolescent and adult states, reflecting an early impairment of these regions. In contrast, biochemical alteration in the Nacc and globus pallidus developed as a matter of age. Our findings suggest that MIS-induced neurochemical and metabolic changes are neurodevelopmental in nature and either progressive or non-progressive and that the behavioral deficits manifest as these abnormalities increase.

Original languageEnglish
Pages (from-to)238-247
Number of pages10
JournalSchizophrenia Research
Volume166
Issue number1-3
DOIs
StatePublished - 5 Jan 2015

Keywords

  • FDG-PET
  • Neurobiological trajectories
  • Neurotransmission
  • Poly I:C
  • Schizophrenia
  • Sensorimotor deficits

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