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Maternal Immune Activation Causes Behavioral Impairments and Altered Cerebellar Cytokine and Synaptic Protein Expression.

ABSTRACT: Emerging epidemiology studies indicate that maternal immune activation (MIA) resulting from inflammatory stimuli such as viral or bacterial infections during pregnancy serves as a risk factor for multiple neurodevelopmental disorders including autism spectrum disorders and schizophrenia. Although alterations in the cortex and hippocampus of MIA offspring have been described, less evidence exists on the impact on the cerebellum. Here, we report altered expression of cytokines and chemokines in the cerebellum of MIA offspring, including increase in the neuroinflammatory cytokine TNF? and its receptor TNFR1. We also report reduced expression of the synaptic organizing proteins cerebellin-1 and GluR?2. These synaptic protein alterations are associated with a deficit in the ability of cerebellar neurons to form synapses and an increased number of dendritic spines that are not in contact with a presynaptic terminal. These impairments are likely contributing to the behavioral deficits in the MIA exposed offspring.

SUBMITTER: Pendyala G

PROVIDER: S-EPMC5436129 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Maternal Immune Activation Causes Behavioral Impairments and Altered Cerebellar Cytokine and Synaptic Protein Expression.

Pendyala Gurudutt G Chou Shinnyi S Jung Yoosun Y Coiro Pierluca P Spartz Elizabeth E Padmashri Ragunathan R Li Ming M Dunaevsky Anna A

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20170119 7

Emerging epidemiology studies indicate that maternal immune activation (MIA) resulting from inflammatory stimuli such as viral or bacterial infections during pregnancy serves as a risk factor for multiple neurodevelopmental disorders including autism spectrum disorders and schizophrenia. Although alterations in the cortex and hippocampus of MIA offspring have been described, less evidence exists on the impact on the cerebellum. Here, we report altered expression of cytokines and chemokines in th ...[more]

PMID: 28102228

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Project description:Maternal immune activation (MIA) has been identified as a significant risk factor for several neurodevelopmental disorders. We have previously demonstrated that postpubertal environmental enrichment (EE) rescues and promotes resiliency against MIA in male rats. Importantly, EE protocols have demonstrated clinical relevancy in human rehabilitation settings. Applying some of the elements of these EE protocols (e.g. social, physical, cognitive stimulation) to animal models of health and disease allows for the exploration of the mechanisms that underlie their success. Here, using a MIA model, we further investigate the rehabilitative potential of complex environments with a focus on female animals. Additionally, we expand upon some of our previous work by exploring genetic markers of synaptic plasticity and stress throughout several brain regions of both sexes. In the current study, standard housed female Sprague-Dawley rats were challenged with either the inflammatory endotoxin lipopolysaccharide (LPS; 100 μg/kg) or saline (equivolume) on gestational day 15. On postnatal day 50, male and female offspring were randomized into one of three conditions that differed in terms of cage size, number of cage mates (social stimulation) and enrichment materials. Spatial discrimination ability and social behavior were assessed six weeks later. Similar to our previously published work in males, our results revealed that a single LPS injection during mid gestation disrupted spatial discrimination ability in female rats. Postpubertal EE rescued this disruption. On the endocrine level, EE dampened elevations in plasma corticosterone that followed MIA, which may mediate EE's rehabilitative effects in female offspring. Within the prefrontal cortex, hippocampus, amygdala, and hypothalamus, MIA and EE altered the mRNA expression of several genes associated with resiliency and synaptic plasticity in both sexes. Overall, our findings provide further evidence that EE may serve as a therapeutic intervention for MIA-induced behavioral and cognitive deficits. Moreover, we identify some sexually dimorphic molecular mechanisms that may underlie these impairments and their rescue.

Dataset Information

Maternal Immune Activation Causes Behavioral Impairments and Altered Cerebellar Cytokine and Synaptic Protein Expression.

Publications

Maternal Immune Activation Causes Behavioral Impairments and Altered Cerebellar Cytokine and Synaptic Protein Expression.

Similar Datasets

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