Expression data from mouse ventral midbrain
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The circadian nature of mood and its dysfunction in affective disorders is well recognized, but the underlying molecular mechanisms are still unclear. We showed that the circadian nuclear receptor REV-ERBa, which is associated with bipolar disorder, impacts midbrain dopamine production and mood-related behavior in mice. Genetic deletion of the Rev-erba gene or pharmacological inhibition of REV-ERBa activity in the ventral midbrain induced mania-like behavior in association with a central hyperdopaminergic state. We used microarrays to identify differentially expressed genes in the ventral midbrains of wild-type (WT) and Rev-erba knock-out (RKO) mice. Male RKO and WT mice (10-15 weeks of age) were maintained in a C57BL/6J background. Mice were housed in temperature-controlled (22-23ºC) quarters under a 12-h light-dark (LD) photoperiod (lights on at 8:00 a.m.). After entrainment for >10 days under LD conditions, mice were kept in constant darkness (DD) for 2 days starting at lights-off time. On the third day, mice were sacrificed at indicated time points by cervical dislocation.
情绪的昼夜节律特性及其在情感障碍中的功能异常已得到广泛认可,但其潜在的分子机制仍不明确。我们发现,与双相情感障碍相关的昼夜节律核受体(circadian nuclear receptor)REV-ERBa可影响小鼠的中脑多巴胺生成与情绪相关行为。在腹侧中脑内敲除Rev-erba基因或通过药物抑制REV-ERBa活性,可诱导产生躁狂样行为,并伴随中枢多巴胺能亢进状态。本研究通过微阵列(microarrays)鉴定了野生型(wild-type,缩写WT)与Rev-erba基因敲除(Rev-erba knock-out,缩写RKO)小鼠腹侧中脑内的差异表达基因。雄性RKO与WT小鼠的周龄为10-15周,均为C57BL/6J遗传背景。小鼠饲养于温度控制在22-23℃的环境中,采用12小时明暗(LD)光周期(光照于上午8:00开启)。在LD光周期环境中适应超过10天后,于关灯时刻起将小鼠置于持续黑暗(DD)环境中2天。于第3天,在指定时间点通过颈椎脱臼法处死小鼠。



