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By: Stacy Zeigler

Sex Differences in the Effects of Acute and Chronic Stress and Recovery after Long-Term Stress on Stress-Related Brain Regions of Rats. By: Stacy Zeigler. Who Cares?. Women more vulnerable to stress-related psychopathologies Depression twice as frequent. CREB and BDNF.

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By: Stacy Zeigler

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  1. Sex Differences in the Effects of Acute and Chronic Stress and Recovery after Long-Term Stress on Stress-Related Brain Regions of Rats By: Stacy Zeigler

  2. Who Cares? • Women more vulnerable to stress-related psychopathologies • Depression twice as frequent

  3. CREB and BDNF • CREB= cAMP response element-binding protein • BDNF TrkB receptor MEK-ERK pathway RSK2 CREB phosphorylation on ser133

  4. Stress • Activate HPA axis • PVN secrete CRF • Anterior pituitary synthesis/release ACTH • Adrenal cortex synthesis/release glucocorticoids • Hippocampus impaired • Behavior, metabolism affected

  5. Sex Differences in the Effects of Acute and Chronic Stress and Recovery after Long-Term Stress on Stress-Related Brain Regions of Rats

  6. Functions • Hippocampus and dAAC • Learning, memory, attention, conflict monitoring, pain, pleasure, decision making • Hippocampus and PFC • Implicated in depression

  7. Sex Differences… • Mechanisms underlying sex differences in stress-related depression • Methods- males/females in each group • 1) No footshock • 2) 6 footshocks on day 42 • 3) Footshocks daily for 3 weeks then no footshocks for 3 weeks • 4) Footshocks daily for 3 weeks; next 3 weeks alternating days of footshocks • 2-4= on day 43 rats exposed to light with no shocks (then killed 2 hrs/30 min after)

  8. Shocked with randomized starting time • unpredictable • 10 second light signal preceded each shock • Examined rat brains • Immunohistochemistry analysis • ELISA and western blot

  9. Males • pCREB in acute and chronic stress groups decreased • CREB in CA2 of acute and chronic stress decreased • Females • No significant changes of pCREB or CREB in stress

  10. Morphological abnormalities in chronic stress group • Patches=very lightly stained; no pCREB- or CREB-positive cells • Females • No patches (not shown) • Males

  11. Males (dAAC) • pCREB levels in chronic stress group decreased and abnormal morphology (black arrow)

  12. Males • pCREB in acute and chronic stress groups decreased • Females • No significant changes of pCREB or CREB in stress

  13. Males • pCREB in acutely stressed group decreased • Females • No significant changes of pCREB or CREB in stress

  14. Males • No significant changes in PL or DG • Females • Decrease in chronic stress of PL of PFC • Increase in acute stress of DG

  15. Discussion • Rat brains response to stress is different • Male/female • Recovery! • reversible • Antidepressants • Shown to increase CREB and pCREB levels in amygdala (Burton et al. 2007)

  16. BDNF Regulation • Regulated by other factors other than pCREB and CREB • Other studies • Nuclear factor of activated T cells (Graef et al. 2003) • mRNA= biphasic time course • Protein= monophasic • 4 different RNA transcripts encode for same BDNF protein • Possible uncoupling of BDNF transcriptional and translational mechanisms

  17. So… • Don’t stress out!!!

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