Po
sttraumati
c stre
ss di
sorder (PTSD) i
s one of the mo
st
common p
sy
chiatri
c di
sorder
s. De
spite the exten
sive
study of the neurobiologi
cal
correlate
s of thi
s di
sorder, the underlying me
chani
sm
s of PTSD are
still poorly under
stood. Re
cently, a
study demon
strated that dexametha
sone (Dex), a
syntheti
c glu
co
corti
coid,
can up-regulate p11, known a
s S100A10-protein whi
ch i
s down-regulated in patient
s with depre
ssion, (
sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0F-4S3S2M9-1&_user=10&_coverDate=06%2F02%2F2008&_rdoc=22&_fmt=full&_orig=browse&_srch=doc-info(%23toc%234861%232008%23998469995%23690665%23FLA%23display%23Volume)&_cdi=4861&_sort=d&_docanchor=&_ct=47&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=345178735facd14e97129828f26060ad#bib28">[Yao et al 1999] and
sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0F-4S3S2M9-1&_user=10&_coverDate=06%2F02%2F2008&_rdoc=22&_fmt=full&_orig=browse&_srch=doc-info(%23toc%234861%232008%23998469995%23690665%23FLA%23display%23Volume)&_cdi=4861&_sort=d&_docanchor=&_ct=47&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=345178735facd14e97129828f26060ad#bib11">[Huang et al 2003]) a
common
comorbid di
sorder in PTSD. The
se ob
servation
s led to our hypothe
si
s that traumati
c stre
ss may alter expre
ssion of p11 mediated through a glu
co
corti
coid re
ceptor. Here, we demon
strate that ine
scapable tail
sho
ck in
crea
sed both prefrontal
corti
cal p11 mRNA level
s and pla
sma
corti
co
sterone level
s in rat
s. We al
so found that Dex up-regulated p11 expre
ssion in SH-SY5Y
cell
s through glu
co
corti
coid re
spon
se element
s (GRE
s) within the p11 promoter. Thi
s re
spon
se wa
s attenuated by either RU486, a glu
co
corti
coid re
ceptor (GR) antagoni
st or mutating two of three glu
co
corti
coid re
spon
se element
s (GRE2 and GRE3) in the p11 promoter. Finally, we
showed that p11 mRNA level
s were in
crea
sed in po
stmortem prefrontal
corti
cal ti
ssue (area 46) of patient
s with PTSD. The data obtained from our work in a rat model of ine
scapable tail
sho
ck, a p11-tran
sfe
cted
cell line and po
stmortem brain ti
ssue from PTSD patient
s outline a po
ssible me
chani
sm by whi
ch p11 i
s regulated by glu
co
corti
coid
s elevated by traumati
c stre
ss.