2.  Women more vulnerable to stress-related psychopathologies  Depression twice as frequent

3.  CREB= cAMP response element-binding protein  BDNF  Trk B receptor  MEK-ERK pathway  RSK2  CREB phosphorylation on ser133

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

11.  Hippocampus and dAAC › Learning, memory, attention, conflict monitoring, pain, pleasure, decision making  Hippocampus and PFC › Implicated in depression

12.  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)

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

16.  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

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

18.  Males (dAAC) › pCREB levels in chronic stress group decreased and abnormal morphology (black arrow)

19.  Males › pCREB in acute and chronic stress groups decreased  Females › No significant changes of pCREB or CREB in stress

20.  Males › pCREB in acutely stressed group decreased  Females › No significant changes of pCREB or CREB in stress

21.  Males › No significant changes in PL or DG  Females › Decrease in chronic stress of PL of PFC › Increase in acute stress of DG

22.  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)

23.  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

24.  Don’t stress out!!!