Kisspeptin modulates gamma-aminobutyric acid levels in the human brain.

Kisspeptin modulates gamma-aminobutyric acid levels in the human brain.
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DOI:
10.1016/j.psyneuen.2021.105244
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发表时间:
2021-07
影响因子:
3.7
通讯作者:
Dhillo WS
Dhillo WS
中科院分区:
医学2区
文献类型:
--
作者:
Comninos AN;Yang L;O'Callaghan J;Mills EG;Wall MB;Demetriou L;Wing VC;Thurston L;Owen BM;Abbara A;Rabiner EA;Dhillo WS

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γ -氨基丁酸(GABA)是一种关键的抑制性神经递质,与常见情绪和行为障碍的病因有关。通过在人体内使用质子磁共振波谱,我们证明了生殖神经肽kisspeptin的管理,强有力地降低GABA水平在人类大脑的边缘系统;特别是前扣带皮层(ACC)。这一发现在人类中定义了一种新的kisspeptin激活的GABA通路,并为kisspeptin在啮齿动物和人类中观察到的情绪和行为改变效应提供了重要的机制见解。此外,这项工作具有治疗意义,因为它确定了gaba信号作为基于kisspeptin的常见身心生殖疾病治疗的潜在靶点。这种名为kisspeptin的神经肽是生殖行为的关键调节器。控制其在人体中的行为作用的分子机制尚不清楚。对19名健康男性给予Kisspeptin或本品。评估前扣带皮层γ -氨基丁酸(GABA)水平。Kisspeptin降低了GABA,一个关键的抑制肽,在这个主要的边缘区域。
Gamma-aminobutyric acid (GABA) is a key inhibitory neurotransmitter that has been implicated in the aetiology of common mood and behavioural disorders. By employing proton magnetic resonance spectroscopy in man, we demonstrate that administration of the reproductive neuropeptide, kisspeptin, robustly decreases GABA levels in the limbic system of the human brain; specifically the anterior cingulate cortex (ACC). This finding defines a novel kisspeptin-activated GABA pathway in man, and provides important mechanistic insights into the mood and behaviour-altering effects of kisspeptin seen in rodents and humans. In addition, this work has therapeutic implications as it identifies GABA-signalling as a potential target for the escalating development of kisspeptin-based therapies for common reproductive disorders of body and mind. The neuropeptide, kisspeptin, is a crucial regulator of reproductive behaviour. The molecular mechanisms that govern its behavioural action in humans are unknown. Kisspeptin or vehicle was administered to 19 healthy men. Anterior cingulate cortex gamma-aminobutyric acid (GABA) levels were assessed. Kisspeptin decreased GABA, a key inhibitory peptide, in this major limbic region.
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