Manganese-enhanced magnetic resonance imaging reveals increased DOI-induced brain activity in a mouse model of schizophrenia

作者: N. V. Malkova , J. J. Gallagher , C. Z. Yu , R. E. Jacobs , P. H. Patterson

DOI: 10.1073/PNAS.1323287111

关键词: Prefrontal cortexAgonistBrain mappingPsychologyNeuroscienceStriatumOffspringNeurotrophic factorsImmediate early geneBrain-derived neurotrophic factorMultidisciplinary

摘要: Maternal infection during pregnancy increases the risk for schizophrenia in offspring. In rodent models, maternal immune activation (MIA) yields offspring with schizophrenia-like behaviors. None of these behaviors are, however, specific to schizophrenia. The presence hallucinations is a key diagnostic symptom mice, this can be defined as brain absence external stimuli, which mimicked by administration hallucinogens. We find that, compared controls, adult MIA display an increased stereotypical behavioral response hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI), agonist serotonin receptor 2A (5-HT2AR). This may explained levels 5-HT2AR and downstream signaling molecules unstimulated prefrontal cortex (PFC). Using manganese-enhanced magnetic resonance imaging identify neuronal elicited DOI administration, we exhibit greater manganese (Mn2+) accumulation several areas, including PFC, thalamus, striatum. parafascicular thalamic nucleus, plays role pathogenesis hallucinations, activated only. Additionally, demonstrate higher DOI-induced expression early growth protein 1, cyclooxygenase-2, brain-derived neurotrophic factor PFC. Chronic treatment antagonist ketanserin reduces head twitching Thus, mouse model successfully used investigate activity induced awake, behaving mice. Moreover, useful, noninvasive method accurately measuring type activity.

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