Enhanced expression of BCL2/adenovirus EIB 19-kDa-interacting protein 3 mRNA, a candidate for intrinsic depression-related factor, and effects of imipramine in the frontal cortex of stressed mice.
We previously reported that long-term treatment with some antidepressants at low concentrations upregulates BCL2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) mRNA expression in NG108-15 cells without causing cell damage, suggesting that BNIP3 is a candidate of intrinsic depressive disorder-related factor(s). In this study, to clarify the physiologic functions of BNIP3, we investigated whether BNIP3 is actually related to the depressive condition in the brain using learned helplessness (LH) mice, an animal model of depression. Based on the score of escape failure, an index of depression degree, stressed animals were divided into groups with LH and without depressive-like symptoms (i.e., non-depressed phenotype, non-LH). The score of escape failure of the LH group was decreased after 14 d of treatment with imipramine in a dose-dependent manner. BNIP3 mRNA expression was enhanced in both the LH and non-LH groups. Imipramine treatment at 5 and 20 mg/kg/d enhanced BNIP3 mRNA expression only in the LH group but not in non-LH group or non-stressed group. These results raise the possibility that BNIP3 acts as an antistress factor in the brain.
Tohda
Michihisa
M
Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, Toyama, Japan. mickey_tonma@yahoo.co.jp
Mingmalairak
Salin
S
Murakami
Yukihisa
Y
Matsumoto
Kinzo
K
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D006380:Helplessness, Learned; D007099:Imipramine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D012333:RNA, Messenger / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D000929:Antidepressive Agents, Tricyclic; C508686:BNip3 protein, mouse; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D007099:Imipramine