THE ROLE OF DNA METHYLATION IN MODULATING CHANGES IN EXPRESSION OF NEUROTROPHIC FACTORS AND MARKERS OF MICROGLIAL ACTIVITY FOLLOWING EARLY-LIFE IMMUNE ACTIVATION IN JUVENILE AND ADULT RATS
Date
2018-05
Authors
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Publisher
University of Delaware
Abstract
Immune activation during early development can have profound effects on
cognitive and behavioral outcomes in adulthood. Epidemiological data indicate a
strong correlation between early-life immune activation and later-life diagnosis with
certain neurodevelopmental disorders including as autism, schizophrenia, and
depression (Maezawa et al., 2011; Frick et al., 2013; O’Connor et al., 2014; Leckman,
2014). Microglia are the resident immune cells of the brain. They are responsible for
phagocytosing cellular debris following infection or injury, and have an active role in
responding to environmental stimuli through the release of various pro- and antiinflammatory
cytokines and neurotrophic factors. Recent findings from our laboratory
have shown that robust immune activation of a juvenile rat (postnatal day 21)
produces a peak response in the expression of the pro-inflammatory cytokine,
Interleukin-1 β (IL-1β), in the hippocampus of juvenile rats within 4 hours. Notably,
this cytokine response is completely resolved within 24 hours; however, rats still
exhibit significant cognitive deficits several days later on postnatal day (P) 24. The
purpose of the experiments is to determine whether changes in the expression
neurotrophic factors in the hippocampus are responsible the cognitive deficits we have
observed on P24, following early-life immune activation, and whether these changes
persist into adulthood. Ongoing experiments will examine whether DNA methylation
could be an underlying mechanism responsible for lasting changes in the expression of
neurotrophic factors and associated cognitive deficits.
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Keywords
Neuroscience, microglia activity, immune activation, DNA methylation