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

Abstract

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.

MicroRNA Expression Is Down-Regulated and Reorganized in Prefrontal Cortex of Depressed Suicide Subjects

“…Among targets that have been experimentally validated ( Table 2 ) and that are co-expressed in prefrontal cortex, at least three (VEGFA, BCL2, and DNA methyltransferase 3B) have been previously implicated in depression or suicide [51], [52], [53]. Of miRNAs that showed the largest and most robust changes in depressed subjects, predicted targets included several brain-active transcription factors such as MITF, SMAD5, MYCN, estrogen receptor alpha (ESR1) and BACH2.…”

Evidence of Antidepressive Effects of aWakan-yaku,Hochuekkito, in Depression Model Mice with Learned-Helplessness Behavior

“…Desipramine, a typical antidepressant, improved the index of depression. We previously reported the similar effect of imipramine [9], whereas the index became worse in water-administered animals with depression. These results suggest that this strategy is highly useful to evaluate the drug effect using the minimal number of animals.…”

“…The paradigm and experimental conditions used to induce LH behavior in mice are the same as previously reported [9]. In the avoidance test conducted on day 4, mice were selected for the experiments as LH animals if escape failed more than 10 times.…”

Whole-genome expression profile in zebrafish embryos after chronic exposure to morphine: identification of new genes associated with neuronal function and mu opioid receptor expression

“…It has interestingly been suggested that mammalian BNIP3 protein can be a candidate for an intrinsic antidepressive effect-related factor and an antistress reaction factor [ 88 , 89 ]. Enhanced Bnip3 expression in NG108-15 cells, which possess the serotonin 2C receptor (5-HT2CR) mRNA system, was observed after exposure to Hochu-ekki-to (HET), a (Wakan-yaku) Sino-Japanese traditional drug with antidepressive effects, as well as after exposure to typical antidepressants [ 88 ].…”