April 12, 2011

OPENING NOTES
-There is one more meeting this semester: Tuesday, April 26 at 7pm in Tobin 521B
-We will be volunteering or just walking at the MS Walk on April 30, so let us know if you're interested in coming
-We still want to make t-shirts and we'll discuss it at the next meeting
-There will be officer elections at the next meeting
-The undergraduate research conference is Friday, April 22

SPEAKER - Elaine Murray, postdoc in Forger lab speaking about "The epigenetics of sex differences in the brain"

Epigenetics
-may account for lack of genetic variability
-alternative explanation for disease susceptibility
-defined as long-lasting changes in gene expression without changing DNA
-DNA methylation and histone modification

Sexual Differentiation
-often due to testosterone exposure during development
-what happens after? epigenetics?
-cells respond to testosterone days to weeks after exposure, have "memory"

Focus on Histone Acetylation
-consistently associated with transcription
-known association with steroid hormone receptor action
-drugs available to inhibit HDAC (in this case, valproic acid or VPA)

Effect of VPA on AcH3 in neonatal mouse brain
-tested at 6, 12, 24, 48, 72, 96 hours after birth and injection of VPA
-AcH3 level was initially higher than normal but lowered by 96 hours

BNSTp (principal nucleus of the bed nucleus of the stria terminalis)
-larger in males
-many more cells in males, but one testosterone injection makes female BNSTp more "male"
-VPA blocks masculinization of the BNSTp in males and masculinized females (treated with an injection of TP), but normal females were not affected
-no effect on non-sexually dimorphic regions

Cell Death in BNSTp
-females have much higher levels of cell death, peaking at postnatal days 5-6
--immunocytochemistry of activated capsase-3, inconclusive results

Sex Differences in Neurochemistry
-vasopressin in lateral septum
-VPA (when injected on postnatal days 1-2 and examined in adulthood) significantly increased vasopressin expression in lateral septum

Behavior
-olfactory preference is sexually dimorphic: males prefer the scent of bedding used by females, and vice versa
-VPA treatment didn't affect behavior much, but it made females spend more time sniffing male AND female bedding

Conclusions
-VPA blocked masculinization of BNSTp but promoted masculinization of vasopressin system and olfactory preference
-testosterone unlikely blocks or promotes gene expression but instead regulates it