Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, KY, USA.
Nat Neurosci. 2024 Sep;27(9):1745-1757. doi: 10.1038/s41593-024-01700-9. Epub 2024 Jul 10.
The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin's dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by these manipulations, indicating independent control of two divergent functions by Purkinje neurons. Our results show that the cerebellum is a thirst-modulating brain area and that asprosin-Ptprd signaling may be a potential therapeutic target for the management of thirst disorders.
小脑，一个从进化上看非常古老的脑区，长期以来一直被认为是严格的运动控制结构。最近的研究表明小脑参与认知、感觉、情绪和自主功能，使其成为进一步研究的重要目标。在这里，我们表明，小鼠小脑浦肯野神经元被激素 asprosin 激活，导致口渴增强，并且光遗传学或化学遗传学激活浦肯野神经元会导致快速出现饮水行为。浦肯野神经元特异性 asprosin 受体（Ptprd）缺失导致水摄入量减少而不影响食物摄入量，并消除了 asprosin 的促饮作用。这些操作对浦肯野神经元介导的运动学习和协调没有影响，表明浦肯野神经元对两种不同功能的独立控制。我们的研究结果表明，小脑是一个调节口渴的脑区，而 asprosin-Ptprd 信号可能是治疗口渴障碍的潜在治疗靶点。
