Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR_S1172, Lille, France.
Physiologie de la Reproduction et des Comportements (PRC) UMR7247 INRA, CNRS, Centre INRAE Val de Loire, IFCE, Université de Tours, Nouzilly, France.
Reprod Domest Anim. 2023 Sep;58 Suppl 2:109-124. doi: 10.1111/rda.14411. Epub 2023 Jul 12.
Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is essential for the activation and maintenance of the function of the hypothalamic-pituitary-gonadal (HPG) axis, which controls the onset of puberty and fertility. Two provocative recent studies suggest that, in addition to control reproduction, the neurons in the brain that produce GnRH are also involved in the control postnatal brain maturation, odour discrimination and adult cognition. Long-acting GnRH antagonists and agonists are commonly used to control fertility and behaviour in veterinary medicine, primarily in males. This review puts into perspective the potential risks of these androgen deprivation therapies and immunization on olfactory and cognitive performances and well-aging in domestic animals, including pets. We will also discuss the results reporting beneficial effects of pharmacological interventions restoring physiological GnRH levels on olfactory and cognitive alterations in preclinical models of Alzheimer's disease, which shares many pathophysiological and behavioural hallmarks with canine cognitive dysfunction. These novel findings raise the intriguing possibility that pulsatile GnRH therapy holds therapeutic potential for the management of this behavioural syndrome affecting older dogs.
脉冲式分泌促性腺激素释放激素（GnRH）对于激活和维持下丘脑-垂体-性腺（HPG）轴的功能至关重要，HPG 轴控制着青春期和生育能力的开始。最近两项有启发性的研究表明，除了控制生殖外，产生 GnRH 的大脑神经元还参与控制出生后大脑成熟、气味辨别和成年认知。长效 GnRH 拮抗剂和激动剂常用于兽医控制生育和行为，主要用于雄性。本综述从潜在风险的角度来看，这些雄激素剥夺疗法和免疫接种对嗅觉和认知表现以及家畜（包括宠物）的衰老的影响。我们还将讨论药理干预恢复生理 GnRH 水平对阿尔茨海默病的临床前模型中嗅觉和认知改变的有益效果的报告结果，该模型与犬认知功能障碍具有许多生理病理学和行为特征。这些新发现提出了一个有趣的可能性，即脉冲 GnRH 治疗可能对管理影响老年犬的这种行为综合征具有治疗潜力。
