Department of Forensic Medicine, University of Pécs Medical School, Szigeti út 12, H-7624 Pécs, Hungary.
Department of Anatomy, HUN-REG-PTE PACAP Research Team, Centre for Neuroscience, University of Pécs Medical School, Szigeti út 12, H-7624 Pécs, Hungary.
Int J Mol Sci. 2023 Oct 11;24(20):15063. doi: 10.3390/ijms242015063.
Sudden infant death syndrome (SIDS) represents a significant cause of post-neonatal mortality, yet its underlying mechanisms remain unclear. The triple-risk model of SIDS proposes that intrinsic vulnerability, exogenous triggers, and a critical developmental period are required for SIDS to occur. Although case-control studies have identified potential risk factors, no in vivo model fully reflects the complexities observed in human studies. Pituitary adenylate cyclase-activating polypeptide (PACAP), a highly conserved neuropeptide with diverse physiological functions, including metabolic and thermal regulation, cardiovascular adaptation, breathing control, stress responses, sleep-wake regulation and immunohomeostasis, has been subject to early animal studies, which revealed that the absence of PACAP or its specific receptor (PAC1 receptor: PAC1R) correlates with increased neonatal mortality similar to the susceptible period for SIDS in humans. Recent human investigations have further implicated PACAP and PAC1R genes as plausible contributors to the pathomechanism of SIDS. This mini-review comprehensively synthesizes all PACAP-related research from the perspective of SIDS and proposes that PACAP deficiency might offer a promising avenue for studying SIDS.
婴儿猝死综合征（SIDS）是新生儿后期死亡的一个重要原因，但其潜在机制尚不清楚。SIDS 的三重风险模型提出，内在脆弱性、外源性触发因素和关键发育阶段是 SIDS 发生所必需的。尽管病例对照研究已经确定了一些潜在的危险因素，但没有任何体内模型能完全反映人类研究中观察到的复杂性。垂体腺苷酸环化酶激活肽（PACAP）是一种高度保守的神经肽，具有多种生理功能，包括代谢和体温调节、心血管适应、呼吸控制、应激反应、睡眠-觉醒调节和免疫稳态，它已经成为早期动物研究的对象，这些研究表明，PACAP 或其特定受体（PAC1 受体：PAC1R）的缺失与新生儿死亡率的增加有关，类似于人类 SIDS 的易感期。最近的人类研究进一步表明，PACAP 和 PAC1R 基因可能是 SIDS 发病机制的合理因素。这篇迷你综述从 SIDS 的角度全面综合了所有与 PACAP 相关的研究，并提出 PACAP 缺乏可能为研究 SIDS 提供一个有前途的途径。
