期刊
SCHIZOPHRENIA RESEARCH
卷 166, 期 1-3, 页码 238-247出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.schres.2015.05.010
关键词
Poly I:C; Schizophrenia; Sensorimotor deficits; FDG-PET; Neurotransmission; Neurobiological trajectories
类别
资金
- Federal Ministry of Education and Research, Germany [BMBF 01EW1103]
- Ministerio de Ciencia e Innovacion [PI11/00616, PI10/02986, PI14/00860 TEC2010-21619-C04-01]
- Comunidad de Madrid
- Fundacion Mapfre
- Canadian Institutes of Health Research
- German Research Foundation [DFG PAK 591 (WI 2140/2-1), DFG KFO 247 (WI 2140/1-1+2)]
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 nonprogressive and that the behavioral deficits manifest as these abnormalities increase. (C) 2015 Elsevier B.V. All rights reserved.
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