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首页> 外文期刊>Neuron >Retinoid x receptor gamma control of affective behaviors involves dopaminergic signaling in mice.
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Retinoid x receptor gamma control of affective behaviors involves dopaminergic signaling in mice.

机译：维甲酸x受体对情感行为的伽玛控制涉及小鼠中的多巴胺能信号传导。

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摘要

Abnormal signaling by retinoids or n-3 polyunsaturated fatty acids has been implicated in clinical depression. The converging point in activities of these two classes of molecules is transcriptional activation of retinoid X receptors (Rxr). We show here that ablation of Rxrgamma in mice leads to depressive-like behaviors including increased despair and anhedonia, which were accompanied by reduced expression of dopamine D2 receptor in the shell of nucleus accumbens (NAc) and altered serotonin signaling. While abnormal serotonin signaling is not sufficient to generate the depressive behaviors, increasing D2r expression by chronic fluoxetine (Prozac) treatment or adenoassociated virus type2 (AAV2) mediated expression of Rxrgamma or D2r in the NAc of Rxrgamma(-/-) mice normalizes depressive-like behaviors in Rxrgamma(-/-) animals. Conversely, NAc infusion of raclopride, a D2r antagonist prevents AAV2-Rxrgamma-mediated rescue of despair behaviors in Rxrgamma(-/-) mice. Combined, our data argue that control of NAc D2r expression is critical for Rxrgamma-mediated modulation of affective behaviors.
机译：类维生素A或n-3多不饱和脂肪酸的异常信号转导与临床抑郁症有关。这两类分子的活性交汇点是类维生素A X受体（Rxr）的转录激活。我们在这里显示，Rxrgamma在小鼠中的消融导致抑郁样行为，包括增加的绝望和快感不足，这伴随着伏伏核（NAc）外壳中多巴胺D2受体的表达减少和血清素信号传导的改变。虽然异常的血清素信号传导不足以产生抑郁行为，但通过慢性氟西汀（Prozac）治疗或腺相关病毒2型（AAV2）介导的Rxrgamma（-/-）小鼠NAc中Rxrgamma或D2r的表达增加D2r表达可使抑郁症正常化。例如Rxrgamma（-/-）动物中的行为。相反，NAc输注雷洛必利，一种D2r拮抗剂可防止AAV2-Rxrgamma介导的Rxrgamma（-/-）小鼠绝望行为的挽救。综合来看，我们的数据表明，NAc D2r表达的控制对于Rxrgamma介导的情感行为调节至关重要。

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