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Page 29
Journal of Clinical Immunology and Allergy
ISSN: 2471-304X
16
th
EuroSciCon Conference on
Immunology
M a r c h 1 1 - 1 2 , 2 0 1 9
Am s t e r d a m , N e t h e r l a n d s
Immunology 2019
O
ffspring of women who drink while pregnant may suffer from fetal alcohol
spectrum disorders (FASD), which includes pervasive and persistent
alterations in behavior and cognition. FASD is modelled in rat pups via
administration of ethanol (5 g/kg/day) over postnatal day 4 to 9, comparable
to the human third trimester. Ethanol induces chronic neuroinflammation in the
developing hippocampus, activating the COX-2 enzyme in microglia and the
release of pro-inflammatory cytokines (e.g., IL-1β). We recently demonstrated
a significant reduction in cytokine gene expression in ethanol-exposed (5E) rats
given ibuprofen (COX-2 inhibitor) concurrent with ethanol and, as adolescents,
amelioration of trace fear conditioning (TFC) memory deficits. Mast cells
(MCs), a novel class of brain-resident immune cells, are also activated by
postnatal ethanol. Indeed, postnatal ethanol induces a significant increase in
the proportion of degranulated MCs and morphologically activated microglia
in the hippocampus of male 5E rats. Both effects are blocked by central
injections of cromolyn, a MC degranulation inhibitor, just prior to daily ethanol
administration. Intriguingly, IL-1β plays a critical role in the maintenance of
NMDA receptor-dependent long-term potentiation (LTP) and the consolidation
of long-term memory. Ethanol-induced inflammation in the neonate brain of
5E rats was hypothesized to enhance hippocampal IL-1β release during TFC,
impeding synaptic plasticity and memory formation. Our most recent findings
confirm this prediction—IL-1β gene and protein expression is elevated in the
hippocampus of male (but not female) 5E rats in the 24 hr period following TFC.
Pre-training administration of Kineret, an IL-1 receptor antagonist, normalized
IL-1β signalling and enhanced long-term memory and TFC test performance
in male 5E rats. Collectively, results signify third trimester-equivalent ethanol
exposure induces chronic hippocampal neuroinflammation leading, in later
life, to aberrant learning-dependent synaptic plasticity and long-term memory
in male, but not female, rodents.
Biography
Lindquist D H has received his PhD in Behavioral Neuroscience
from Yale University in 2004. Following Postdoctoral Work
at Indiana University and the University of Kansas, he joined
the Psychology department at The Ohio State University
in 2010. Over his career, he has published approximately
20 papers in reputed Neuroscience journals related to the
neurobiology learning and memory, neurodevelopment and
neuroinflammation.
lindquist.40@osu.eduPostnatal ethanol exposure induces chronic
neuroinflammation and impedes hippocampal-dependent
synaptic plasticity and long-term memory in adolescent rats
Lindquist D H
1,2
, Dause T J
1
, Pochio J M
2
and Goodfellow M J
1
The Ohio State University
Lindquist D H et al., J Clin Immunol Allergy 2019, Volume:5
DOI: 10.21767/2471-304X-C1-008