Posttrau
matic stress disorder (PTSD) is one o
f the
most co
mmon psychiatric disorders. Despite the extensive study o
f the neurobiological correlates o
f this disorder, the underlying
mechanis
ms o
f PTSD are still poorly understood. Recently, a study de
monstrated that dexa
methasone (Dex), a synthetic glucocorticoid, can up-regulate p11, known as S100A10-protein which is down-regulated in patients with depression, (
me="bbib28">f="http://www.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
me="bbib11">f="http://www.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 co
mmon co
morbid disorder in PTSD. These observations led to our hypothesis that trau
matic stress
may alter expression o
f p11
mediated through a glucocorticoid receptor. Here, we de
monstrate that inescapable tail shock increased both pre
frontal cortical p11
mRNA levels and plas
ma corticosterone levels in rats. We also
found that Dex up-regulated p11 expression in SH-SY5Y cells through glucocorticoid response ele
ments (GREs) within the p11 pro
moter. This response was attenuated by either RU486, a glucocorticoid receptor (GR) antagonist or
mutating two o
f three glucocorticoid response ele
ments (GRE2 and GRE3) in the p11 pro
moter. Finally, we showed that p11
mRNA levels were increased in post
morte
m pre
frontal cortical tissue (area 46) o
f patients with PTSD. The data obtained
fro
m our work in a rat
model o
f inescapable tail shock, a p11-trans
fected cell line and post
morte
m brain tissue
fro
m PTSD patients outline a possible
mechanis
m by which p11 is regulated by glucocorticoids elevated by trau
matic stress.