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Sex Differences in Acute and Chronic Stress Effects on Rat Brain Regions and Recovery Mechanisms

This study explores how acute and chronic stress impacts male and female rats differently, focusing on stress-related brain regions. It highlights that women may be more susceptible to stress-induced psychopathologies, with depression occurring twice as often in females. The study examines mechanisms like CREB and BDNF pathways, revealing significant sex differences in the brain's response to stress, recovery from long-term stress, and implications for future treatment of stress-related disorders. Understanding these differences is crucial for developing gender-specific interventions.

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Sex Differences in Acute and Chronic Stress Effects on Rat Brain Regions and Recovery Mechanisms

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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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