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The Mood‐Stabilizing Agents Lithium and Valproate RobustlIncrease the Levels of the Neuroprotective Protein bcl‐2 in the CNS
Author(s) -
Chen Guang,
Zeng WeiZhang,
Yuan PeiXiong,
Huang LiDong,
Jiang YiMing,
Zhao ZhenHua,
Manji Husseini K.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.720879.x
Subject(s) - neuroprotection , valproic acid , transcription factor , lithium (medication) , mood , mood disorders , messenger rna , medicine , pharmacology , endocrinology , neuroscience , biology , chemistry , gene , psychiatry , genetics , epilepsy , anxiety
: Differential display of mRNA was used to identify concordant changes in gene expression induced by two mood‐stabilizing agents, lithium and valproate (VPA). Both treatments, on chronic administration, increased mRNA levels of the transcription factor polyomavirus enhancer‐binding protein (PEBP) 2β in frontal cortex (FCx). Both treatments also increased the DNA binding activity of PEBP2αβ and robustly increased the levels of bcl‐2 (known to be transcriptionally regulated by PEBP2) in FCx. Immunohistochemical studies revealed a marked increase in the number of bcl‐2‐immunoreactive cells in layers 2 and 3 of FCx. These novel findings represent the first report of medication‐induced increases in CNS bcl‐2 levels and may have implications not only for mood disorders, but also for long‐term treatment of various neurodegenerative disorders.