近日，
研究人员在一个唐氏综合征（DS）模型（Ts65Dn小鼠）中发现，这些进行性的非生殖性神经症状与青春期后下丘脑以及下丘脑外控制生殖的核心分子--促性腺激素释放激素（GnRH）的表达减少密切相关，并且似乎与已知调节GnRH神经元成熟的microRNA-基因网络的不平衡以及海马突触传递的改变有关。
通过表观遗传学、细胞学、化学遗传学和药理学干预， GnRH生理水平的恢复减少了Ts65Dn小鼠的嗅觉和认知缺陷，而脉冲式GnRH治疗改善了成年DS患者的认知和大脑连接。因此，GnRH在嗅觉和认知方面起着至关重要的作用，脉冲式GnRH疗法有希望改善DS的认知缺陷。
据悉，目前对于DS的认知和嗅觉障碍还没有可行的治疗方法。
附：英文原文
Title: GnRH replacement rescues cognition in Down syndrome
Author: Maria Manfredi-Lozano, Valerie Leysen, Michela Adamo, Isabel Paiva, Renaud Rovera, Jean-Michel Pignat, Fatima Ezzahra Timzoura, Michael Candlish, Sabiha Eddarkaoui, Samuel A. Malone, Mauro S. B. Silva, Sara Trova, Monica Imbernon, Laurine Decoster, Ludovica Cotellessa, Manuel Tena-Sempere, Marc Claret, Ariane Paoloni-Giacobino, Damien Plassard, Emmanuelle Paccou, Nathalie Vionnet, James Acierno, Aleksandra Maleska Maceski, Antoine Lutti, Frank Pfrieger, S. Rasika, Federico Santoni, Ulrich Boehm, Philippe Ciofi, Luc Buée, Nasser Haddjeri, Anne-Laurence Boutillier, Jens Kuhle, Andrea Messina, Bogdan Draganski, Paolo Giacobini, Nelly Pitteloud, Vincent Prevot
Issue&Volume: 2022-09-02
Abstract: At the present time, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show in a DS model (Ts65Dn mice) that these progressive nonreproductive neurological symptoms closely parallel a postpubertal decrease in hypothalamic as well as extrahypothalamic expression of a master molecule that controls reproduction—gonadotropin-releasing hormone (GnRH)—and appear related to an imbalance in a microRNA-gene network known to regulate GnRH neuron maturation together with altered hippocampal synaptic transmission. Epigenetic, cellular, chemogenetic, and pharmacological interventions that restore physiological GnRH levels abolish olfactory and cognitive defects in Ts65Dn mice, whereas pulsatile GnRH therapy improves cognition and brain connectivity in adult DS patients. GnRH thus plays a crucial role in olfaction and cognition, and pulsatile GnRH therapy holds promise to improve cognitive deficits in DS.
DOI: abq4515
Source: https://www.science.org/doi/10.1126/science.abq4515