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Schizophr Res. 2015 Aug;166(1-3):238-47. doi: 10.1016/j.schres.2015.05.010. Epub 2015 Jun 6.

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

Author information

1
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany.
2
Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
3
Centre for Addiction and Mental Health, Division of Neurosurgery, University of Toronto, Toronto, Canada.
4
School of Psychological Sciences and Sagol School of NeuroscienceTel-Aviv UniversityTel-Aviv, Israel.
5
Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain.
6
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany. Electronic address: christine.winter@uniklinikum-dresden.de.

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.

KEYWORDS:

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

PMID:
26055633
PMCID:
PMC5233455
DOI:
10.1016/j.schres.2015.05.010
[Indexed for MEDLINE]
Free PMC Article

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