Department of Comparative Medicine, 12228Yale University School of Medicine, New Haven, CT, USA.
Toxicol Pathol. 2021 Dec;49(8):1368-1373. doi: 10.1177/01926233211046933. Epub 2021 Sep 26.
Within the substantially different time scales characterizing human and rodent brain development, key developmental processes are remarkably preserved. Shared processes include neurogenesis, myelination, synaptogenesis, and neuronal and synaptic pruning. In general, altricial rodents experience greater central nervous system (CNS) immaturity at birth and accelerated postnatal development compared to humans, in which protracted development of certain processes such as neocortical myelination and synaptic maturation extend into adulthood. Within this generalization, differences in developmental rates of various structures must be understood to accurately model human neurodevelopmental toxicity in rodents. Examples include greater postnatal neurogenesis in rodents, particularly within the dentate gyrus of rats, ongoing generation of neurons in the rodent olfactory bulb, differing time lines of neurotransmitter maturation, and differing time lines of cerebellar development. Comparisons are made to the precocial guinea pig and the long-lived naked mole rat, which, like primates, experiences more advanced CNS development at birth, with more protracted postnatal development. Methods to study various developmental processes are summarized using examples of comparative postnatal injury in humans and rodents.
在人类和啮齿动物大脑发育的时间尺度上存在显著差异,但关键的发育过程却惊人地相似。共同的过程包括神经发生、髓鞘形成、突触形成以及神经元和突触修剪。一般来说,与人类相比,晚成性啮齿动物在出生时中枢神经系统(CNS)发育不成熟,并且出生后发育速度更快,其中某些过程如大脑新皮质髓鞘形成和突触成熟的延长发育会持续到成年期。在这种概括中,必须理解各种结构的发育速度差异,才能准确地在啮齿动物中模拟人类神经发育毒性。例如,啮齿动物在出生后有更多的神经发生,特别是在大鼠的齿状回中,在啮齿动物的嗅球中仍有神经元生成,神经递质成熟的时间不同,以及小脑发育的时间不同。与早熟的豚鼠和长寿的裸鼹鼠进行了比较,它们与灵长类动物一样,在出生时具有更先进的中枢神经系统发育,并且出生后发育时间更长。使用人类和啮齿动物的比较性出生后损伤的例子,总结了研究各种发育过程的方法。