Viral-mediated Zif268 expression in the prefrontal cortex protects against gonadectomy-induced working memory, long-term memory, and social interaction deficits in male rats.
Viral-mediated Zif268 expression in the prefrontal cortex protects against gonadectomy-induced working memory, long-term memory, and social interaction deficits in male rats.
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病毒介导的ZIF268在前额叶皮层中的表达可预防雄性大鼠的性腺切除术引起的工作记忆，长期记忆和社交相互作用缺陷。
DOI：
10.1016/j.neuroscience.2016.10.062
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发表时间：
2017-01-06
期刊：
影响因子：
3.3
通讯作者：
Kabbaj M
中科院分区：
文献类型：
--
作者：
Dossat AM;Jourdi H;Wright KN;Strong CE;Sarkar A;Kabbaj M
在人类中，一些男性会经历睾丸激素水平的下降，这是衰老的自然结果，或者是性腺功能减退的临床症状，这与认知能力受损和情绪障碍有关。其中一些行为缺陷可以通过睾酮治疗逆转。我们之前在大鼠身上的研究表明，在内侧前额叶皮层（mPFC）中，转录因子Zif268（睾酮的下游靶点）的表达存在性别差异，介导了社会互动中的性别差异。在本研究中，我们旨在研究性腺切除术（GNX）对雄性大鼠mPFC Zif268表达、情绪和认知行为的影响。我们还研究了在GNX大鼠中重新使用Zif268是否会纠正GNX后观察到的一些行为缺陷。我们的研究结果表明，GNX诱导mPFC中Zif268蛋白下调，并伴有y形迷宫和自发物体识别测试中的记忆受损，社交互动时间减少以及强迫游泳测试中的抑郁样行为。使用一种新的腺相关病毒（AAV）构建物重建mPFC Zif268，可以消除gnx诱导的工作记忆和长期记忆障碍，并减少社交互动时间，但不能消除gnx诱导的抑郁样行为。这些发现表明mPFC Zif268对记忆和社会互动有有益的影响，可能是性腺功能低下和性腺激素水平下降的老年男性行为障碍的新治疗方法的潜在靶点。
In humans, some males experience reductions in testosterone levels, as a natural consequence of aging or in the clinical condition termed hypogonadism, which are associated with impaired cognitive performance and mood disorder(s). Some of these behavioral deficits can be reversed by testosterone treatment. Our previous work in rats reported that sex differences in the expression of the transcription factor Zif268, a downstream target of testosterone, within the medial prefrontal cortex (mPFC) mediates sex differences in social interaction. In the present study, we aimed to examine the effects of gonadectomy (GNX) in male rats on mPFC Zif268 expression, mood and cognitive behaviors. We also examined whether reinstitution of Zif268 in GNX rats will correct some of the behavioral deficits observed following GNX. Our results show that GNX induced a downregulation of Zif268 protein in the mPFC, which was concomitant with impaired memory in the y-maze and spontaneous object recognition test, reduced social interaction time, and depression-like behaviors in the forced swim test. Reinstitution of mPFC Zif268, using a novel adeno-associated-viral (AAV) construct, abrogated GNX-induced working memory and long-term memory impairments, and reductions in social interaction time, but not GNX-induced depression-like behaviors. These findings suggest that mPFC Zif268 exerts beneficial effects on memory and social interaction, and could be a potential target for novel treatments for behavioral impairments observed in hypogonadal and aged men with declining levels of gonadal hormones.
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影响因子：
3.7
作者：
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通讯作者：
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