Women more vulnerable to stress-related psychopathologies Depression twice as frequent.
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Transcript of Women more vulnerable to stress-related psychopathologies Depression twice as frequent.
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Women more vulnerable to stress-related psychopathologies
Depression twice as frequent
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CREB= cAMP response element-binding protein
BDNF TrkB receptor MEK-ERK pathway RSK2 CREB phosphorylation on ser133
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Activate HPA axis PVN secrete CRF Anterior pituitary
synthesis/release ACTH
Adrenal cortex synthesis/release glucocorticoids
Hippocampus impaired
Behavior, metabolism affected
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Hippocampus and dAAC› Learning, memory, attention, conflict
monitoring, pain, pleasure, decision making
Hippocampus and PFC› Implicated in depression
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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)
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Shocked with randomized starting time› unpredictable
10 second light signal preceded each shock
Examined rat brains› Immunohistochemistry analysis› ELISA and western blot
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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
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Males› Morphological
abnormalities in chronic stress group
› Patches=very lightly stained; no pCREB- or CREB-positive cells
Females No patches
(not shown)
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Males (dAAC)› pCREB levels
in chronic stress group decreased and abnormal morphology (black arrow)
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Males› pCREB in
acute and chronic stress groups decreased
Females› No significant
changes of pCREB or CREB in stress
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Males› pCREB in
acutely stressed group decreased
Females› No significant
changes of pCREB or CREB in stress
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Males› No significant
changes in PL or DG
Females› Decrease in
chronic stress of PL of PFC
› Increase in acute stress of DG
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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)
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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
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Don’t stress out!!!