关于小头畸形和 GnRH 的新见解:对神经发育、认知和 COVID-19 疗法的影响

IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Konstantina Chachlaki, Kevin Le Duc, Laurent Storme, Vincent Prevot
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引用次数: 0

摘要

人类出生后的头 1000 天是大脑和机体发育的关键时期。出生后不久,下丘脑中的促性腺激素释放激素(GnRH)神经元就被激活,这种现象被称为 "小青春期"。在研究的所有哺乳动物中都能观察到这种现象,它影响着下丘脑-垂体-性腺轴(HPG)的产后发育和生殖功能。本综述将介绍最近的研究结果,这些研究结果表明,小头畸形的影响超出了生殖功能,还会影响感官和认知的成熟。对小鼠的研究揭示了一氧化氮(NO)在调节小脑发育期振幅中的作用,缺乏一氧化氮与认知和嗅觉缺陷有关。此外,研究结果表明,唐氏综合征小鼠模型成年后的认知和感官缺陷与随年龄增长而下降的GnRH分泌有关,而GnRH分泌的起源可追溯到小脑发育期,研究结果还指出了脉冲性GnRH给药对认知障碍的潜在治疗作用。此外,本综述还深入探讨了 COVID-19 对 GnRH 分泌的影响,强调了对受感染者神经发育和认知功能的潜在后果。值得注意的是,GnRH神经元似乎易受SARS-CoV-2感染,从而引发了对大脑发育和功能潜在长期影响的担忧。总之,GnRH 神经元、GnRH 释放和各种下丘脑外脑回路的活动之间错综复杂的相互作用揭示了这些神经内分泌神经元在感官和认知功能的发育和维持中发挥着意想不到的作用,补充了它们在生殖方面的既有功能。针对 HPG 轴的治疗干预,如婴儿期的吸入性 NO 治疗和成人期的脉冲性 GnRH 给药,有望成为解决神经发育认知障碍和病理衰老的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Novel insights into minipuberty and GnRH: Implications on neurodevelopment, cognition, and COVID-19 therapeutics

Novel insights into minipuberty and GnRH: Implications on neurodevelopment, cognition, and COVID-19 therapeutics

Novel insights into minipuberty and GnRH: Implications on neurodevelopment, cognition, and COVID-19 therapeutics

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.

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来源期刊
Journal of Neuroendocrinology
Journal of Neuroendocrinology 医学-内分泌学与代谢
CiteScore
6.40
自引率
6.20%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Journal of Neuroendocrinology provides the principal international focus for the newest ideas in classical neuroendocrinology and its expanding interface with the regulation of behavioural, cognitive, developmental, degenerative and metabolic processes. Through the rapid publication of original manuscripts and provocative review articles, it provides essential reading for basic scientists and clinicians researching in this rapidly expanding field. In determining content, the primary considerations are excellence, relevance and novelty. While Journal of Neuroendocrinology reflects the broad scientific and clinical interests of the BSN membership, the editorial team, led by Professor Julian Mercer, ensures that the journal’s ethos, authorship, content and purpose are those expected of a leading international publication.
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