The common aspects of pathophysiolgy of alcoholism and depression.
Recent biological studies suggest the existence of the common pathophysiological aspects in alcoholism and depression. Postmortem studies have revealed the impairment of cAMP signaling in the patients with alcoholism. The similar alteration of cAMP signaling was also reported in postmortem brains of depressed patients. In this study, we supported the notion that neurogenesis would be essential in pathophysiology of both alcoholism and depression. Alcohol affected the function of neural stem cells (NSCs) and decreased neurogenesis at doses which did not affects cell survival, and treatment of antidepressant or moodstabilizer rescued the alcohol-induced suppression of neurogenesis. As the key mechanism of NSC differentiation change by ethanol and psychotropics, we focused on the transcriptional repressor, NRSF/REST activity change. Our in vitro studies demonstrated the NRSF/REST activation by ethanol and suppressive effect of antidepressants and lithium against its activation by ethanol. We further described the ERK reduction and ER stress in the cellular mechanism of NRSF/REST activation. All these findings suggested that cAMP-CREB cascade reduction and NRSF/REST activation may be common underlying mechanisms in the pathophysiology of alcoholism and depression.
Ukai
Wataru
W
Department of Neuropsychiatry, Sapporo Medical University, School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543 Japan.
Ishii
Takao
T
Hashimoto
Eri
E
Tateno
Masaru
M
Yoshinaga
Toshihiro
T
Ono
Takafumi
T
Watanabe
Kimihiko
K
Watanabe
Ippei
I
Shirasaka
Tomohiro
T
Saito
Toshikazu
T
D000437:Alcoholism / Q000209:etiology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D003863:Depression / Q000209:etiology*; D004721:Endoplasmic Reticulum / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D018020:Lithium Compounds / Q000494:pharmacology; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology; D051381:Rats; D012097:Repressor Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D000099229:RE1-Silencing Transcription Factor
D000928:Antidepressive Agents; D000242:Cyclic AMP; D017362:Cyclic AMP Response Element-Binding Protein; D000431:Ethanol; D048049:Extracellular Signal-Regulated MAP Kinases; D018020:Lithium Compounds; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor