Abstract：
In humans, the first 1000 days of life are pivotal for brain and organism development. Shortly after birth, gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus are activated, a phenomenon known as minipuberty. This phenomenon, observed in all mammals studied, influences the postnatal development of the hypothalamic-pituitary-gonadal (HPG) axis and reproductive function. This review will put into perspective the results of recent studies showing that the impact of minipuberty extends beyond reproductive function, influencing sensory and cognitive maturation. Studies in mice have revealed the role of nitric oxide (NO) in regulating minipuberty amplitude, with NO deficiency linked to cognitive and olfactory deficits. Additionally, findings indicate that cognitive and sensory defects in adulthood in a mouse model of Down syndrome are associated with an age-dependent decline of GnRH production, whose origin can be traced back to minipuberty, and point to the potential therapeutic role of pulsatile GnRH administration in cognitive disorders. Furthermore, this review delves into the repercussions of COVID-19 on GnRH production, emphasizing potential consequences for neurodevelopment and cognitive function in infected individuals. Notably, GnRH neurons appear susceptible to SARS-CoV-2 infection, raising concerns about potential long-term effects on brain development and function. In conclusion, the intricate interplay between GnRH neurons, GnRH release, and the activity of various extrahypothalamic brain circuits reveals an unexpected role for these neuroendocrine neurons in the development and maintenance of sensory and cognitive functions, supplementing their established function in reproduction. Therapeutic interventions targeting the HPG axis, such as inhaled NO therapy in infancy and pulsatile GnRH administration in adults, emerge as promising approaches for addressing neurodevelopmental cognitive disorders and pathological aging.
摘要：
在人类中,生命的前1000天是大脑和机体发育的关键。出生后不久,下丘脑中的促性腺激素释放激素（GnRH）神经元被激活，一种被称为小青春期的现象。这种现象,在所有研究的哺乳动物中观察到，影响下丘脑-垂体-性腺（HPG）轴的发育和生殖功能。这篇综述将透视最近的研究结果，表明小青春期的影响超出了生殖功能，影响感官和认知成熟。对小鼠的研究揭示了一氧化氮（NO）在调节青春期振幅中的作用，NO缺乏与认知和嗅觉缺陷有关。此外,研究结果表明，在唐氏综合征小鼠模型中，成年期的认知和感觉缺陷与GnRH产生的年龄依赖性下降有关，其起源可以追溯到小青春期，并指出脉冲式GnRH给药在认知障碍中的潜在治疗作用。此外，这篇评论探讨了COVID-19对GnRH生产的影响，强调对感染个体的神经发育和认知功能的潜在影响。值得注意的是,GnRH神经元似乎易受SARS-CoV-2感染，引起人们对大脑发育和功能的潜在长期影响的担忧。总之,GnRH神经元之间复杂的相互作用，GnRH释放，各种下丘脑外脑回路的活动揭示了这些神经内分泌神经元在感觉和认知功能的发育和维持中的意想不到的作用，补充它们在繁殖中的既定功能。针对HPG轴的治疗干预措施，如婴儿期吸入NO治疗和成人脉冲GnRH给药，成为解决神经发育性认知障碍和病理性衰老的有希望的方法。
