BIOC14 : Lec 19

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Biological Sciences
Patrick Mc Gowan

BIOC14Lec 19y HPA axis o Negative feedback loop o Look at brain diagram for the HPA axis o Loophow feedback is controlled during stressful response have corticosteroid receptors and these are all over the brain but the effects of HPA axis are thru certain loops of the brain that includes both the hippo and hypothalamus o So when you have stressful experience your stress response involves the release of adrenocorticotropin releasing hormone from the pituitary and this causes cortisol release from adrenal cortexcortisol in bloodstreamfeeds back up to the brain and acts on the glucocorticoid receptors acts both on hypothalamus and hippoactivities at the levels of the 2 diff loops DO DIFF THINGSWere interested in activity in hippo bc were interested in explaining like anxiety and deprelated to hippocampal fxnBut works at multiple levels of the loopCortisol acts on glucocorticoid receptorssends a signal back to hypothalamusdownregulates further adrenocorticotropin releasing hormone from pituitaryOVERALL have downregulation of adrenocorticotropin releasing hormone downregulation of cortisol and downregulation of stress responseWhat determines how strong the stress response is going to be involves how many glucocorticoid receptors you have y The more receptors you have the quicker you can shut down the response bc theres more sites for cortisol to bindo Involvement of hippo in stress and anxiety behinvolves regulation of the s of glucocorticoid receptors o More receptorsquicker you can shut down response o Things that regulate theof receptors will regulate the peak response to stress and how stressful an event will be happens in rodentshumansgreat model to study physiological responses associated with anxiety o Factors that affect glucocorticoid receptor distribution is related in terms of early life events and their impact on regulating the s of these receptors expression of the glucocorticoid receptor gene in hippoother brain areas alsoo Early maternal care in animal model we quantify amount of lickinggrooming beh of mother on offspring o This behnormally distributed in rats take tail ends of this distributionhigh and low end lickers o Data shows that the amount of licking that pup receives determines the levels of glucocorticoid gene expression and their response to stress in adulthood takes 21d to wean ratsable to eat on their ownadults90d o In adulthood and throughout life theof glucocorticoid receptors seem to be the samestable o In terms of regulation of this receptor it seemed to involve DNA methylation of promoter region of this gene that blocked transcription factors that were regulating the expression of glucocorticoid receptorThese differences in methylation that are associated with gene expression develop during the first week of life of pups when they receive most of the maternal care that theyll ever get in lifeDifferences in expression and differences in methylation are very stable across the lifespanPharmacological manipulation that could alter thisWhat other kinds of manipulations can alter this methylation patternHow stable is it really Dont know very well think that if you give animal very enriched environment stimulating toys social other ratscan reverse some of the behavioral effects of the difference in maternal care can reverse some of the effects of glucocorticoid receptor expressiondont know how its tied to changes in epigenetic signature yetCould traumatic effect later in life switch the highly licked animal very resistant to stress less anxious to a more anxious animal Model of PTSD
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