Regulation of ER stress proteins by valproate: therapeutic implications.
OBJECTIVE
This paper reviews results of our studies examining the regulation of endoplasmic reticulum (ER) stress proteins by valproate (VPA). and discusses the possible implications in bipolar disorder.


METHODS
Our previous studies in the field are reviewed along with relevant literature.


RESULTS
Using differential display PCR, we identified GRP78 as a VPA-regulated gene in rat cerebral cortex. We also showed that other members of the ER stress proteins family, GRP94 and calreticulin, are also upregulated by VPA. Immunohistochemistry identified that ER stress proteins are increased in frontal and parietal cortex, as well as regions of the hippocampus in rat brain following chronic treatment with VPA.


CONCLUSIONS
Regulation of ER stress proteins by VPA may prove to be important to the mechanism of action of the drug. The neuroprotective role of these proteins may also prove to be involved in the pathophysiology of bipolar disorder.
Bown
Christopher D
CD
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Wang
Jun-Feng
JF
Chen
Biao
B
Young
L Trevor
LT
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use*
D000928:Antidepressive Agents; D006360:Heat-Shock Proteins; D014635:Valproic Acid