title: Mood stabilizers commonly restore staurosporine-induced increase of p53 expression and following decrease of Bcl-2 expression in SH-SY5Y cells.
abstract: Adult neurogenesis in dentate gyrus (DG) is involved in the action mechanism of mood stabilizers. However, it is poorly understood how mood stabilizers affect adult neurogenesis in DG. Neurogenesis consists of proliferation, survival (anti-apoptosis) and differentiation of neural precursor cells in adult DG. Using in vitro culture of adult rat DG-derived neural precursor cells (ADP), we have already shown that four mood stabilizers, such as lithium (Li), valproate (VPA), carbamazepine (CBZ) and lamotrigine (LTG), commonly decrease staurosporine (STS)-induced apoptosis of ADP. These suggest that the common anti-apoptotic effect of mood stabilizers could be involved in mood-stabilizing effects. Past studies have shown that Li and VPA increase the expression of Bcl-2, an anti-apoptotic gene. In addition, it has been shown that Li decreases the expression of p53, which plays a prominent role in apoptosis and regulates the expression of Bcl-2. Therefore, p53 and Bcl-2 can be considered to mediate the common anti-apoptotic effects of Li, VPA, CBZ and LTG. To elucidate the molecular mechanism underlying the common anti-apoptotic effects of mood stabilizers, we investigated the effects of Li, VPA, CBZ and LTG on STS-induced expression changes of p53, Bcl-2 and other p53-related molecules using SH-SY5Y cells as a model of neural precursor-like cells. STS increased the expression of p53 and decreased that of Bcl-2. These effects of STS on p53 and Bcl-2 are restored by all of Li, VPA, CBZ and LTG. In addition, p53 overexpression decreased the expression of Bcl-2. Taken together, these results suggest that p53 and Bcl-2 may be involved in a part of mood-stabilizing effects.
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Ning
authors.initials: N
authors.lastname: Song
authors.forename: Shuken
authors.initials: S
authors.lastname: Boku
authors.forename: Shin
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Kato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Toda
authors.forename: Naoki
authors.initials: N
authors.lastname: Takamura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Omiya
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kitaichi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Koyama
mesh_terms: D018692:Antimanic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002220:Carbamazepine / Q000494:pharmacology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D000077213:Lamotrigine; D008094:Lithium / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology*; D014227:Triazines / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D018692:Antimanic Agents; D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D014227:Triazines; D016159:Tumor Suppressor Protein p53; D002220:Carbamazepine; D014635:Valproic Acid; D008094:Lithium; D019311:Staurosporine; D000077213:Lamotrigine