Women more vulnerable to stress-related psychopathologies

Depression twice as frequent

CREB= cAMP response element-binding protein

BDNF TrkB receptor MEK-ERK pathway RSK2 CREB phosphorylation on ser133

Activate HPA axis PVN secrete CRF Anterior pituitary

synthesis/release ACTH

Adrenal cortex synthesis/release glucocorticoids

Hippocampus impaired

Behavior, metabolism affected

Hippocampus and dAAC› Learning, memory, attention, conflict

monitoring, pain, pleasure, decision making

Hippocampus and PFC› Implicated in depression

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)

Shocked with randomized starting time› unpredictable

10 second light signal preceded each shock

Examined rat brains› Immunohistochemistry analysis› ELISA and western blot

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

Males› Morphological

abnormalities in chronic stress group

› Patches=very lightly stained; no pCREB- or CREB-positive cells

Females No patches

(not shown)

Males (dAAC)› pCREB levels

in chronic stress group decreased and abnormal morphology (black arrow)

Males› pCREB in

acute and chronic stress groups decreased

Females› No significant

changes of pCREB or CREB in stress

Males› pCREB in

acutely stressed group decreased

Females› No significant

changes of pCREB or CREB in stress

Males› No significant

changes in PL or DG

Females› Decrease in

chronic stress of PL of PFC

› Increase in acute stress of DG

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)

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

Don’t stress out!!!