women more vulnerable to stress-related psychopathologies depression twice as frequent
TRANSCRIPT
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!!!