La Rosa Chiara, Bonfanti Luca
Neuroscience Institute Cavalieri Ottolenghi, Turin, Italy.
Department of Veterinary Sciences, University of Turin, Turin, Italy.
Front Vet Sci. 2018 Nov 1;5:274. doi: 10.3389/fvets.2018.00274. eCollection 2018.
Comparative medicine deals with similarities and differences between veterinary and human medicine. All mammals share most basic cellular and molecular mechanisms, thus justifying murine animal models in a translational perspective; yet "mice are not men," thus some biases can emerge when complex biological processes are concerned. Brain plasticity is a cutting-edge, expanding topic in the field of Neurosciences with important translational implications, yet, with remarkable differences among mammals, as emerging from comparative studies. In particular, adult neurogenesis (the genesis of new neurons from brain stem cell niches) is a life-long process in laboratory rodents but a vestigial, mostly postnatal remnant in humans and dolphins. Another form of "whole cell" plasticity consisting of a population of "immature" neurons which are generated prenatally but continue to express markers of immaturity during adulthood has gained interest more recently, as a reservoir of young neurons in the adult brain. The distribution of the immature neurons also seems quite heterogeneous among different animal species, being confined within the paleocortex in rodents while extending into neocortex in other mammals. A recent study carried out in sheep, definitely showed that gyrencephalic, large-sized brains do host higher amounts of immature neurons, also involving subcortical, white, and gray matter regions. Hence, "whole cell" plasticity such as adult neurogenesis and immature neurons are biological processes which, as a whole, cannot be studied exclusively in laboratory rodents, but require investigation in comparative medicine, involving large-sized, long-living mammals, in order to gain insights for translational purposes.
比较医学研究兽医学与人类医学之间的异同。所有哺乳动物都具有大多数基本的细胞和分子机制,因此从转化医学的角度来看,鼠类动物模型是合理的;然而,“小鼠不是人类”,因此在涉及复杂生物过程时可能会出现一些偏差。脑可塑性是神经科学领域一个前沿且不断扩展的主题,具有重要的转化意义,然而,从比较研究中可以看出,哺乳动物之间存在显著差异。特别是,成体神经发生(从脑干细胞龛产生新神经元)在实验啮齿动物中是一个终身过程,但在人类和海豚中是一种退化的、主要在出生后残留的现象。另一种“全细胞”可塑性形式是由一群“未成熟”神经元组成,这些神经元在产前产生,但在成年期仍继续表达未成熟标记,最近作为成年大脑中年轻神经元的储存库受到了更多关注。未成熟神经元的分布在不同动物物种之间似乎也相当不均匀,在啮齿动物中局限于古皮质,而在其他哺乳动物中延伸到新皮质。最近在绵羊身上进行的一项研究明确表明,脑回状的大型大脑确实含有大量未成熟神经元,也涉及皮质下、白质和灰质区域。因此,诸如成体神经发生和未成熟神经元等“全细胞”可塑性是生物学过程,总体而言,不能仅在实验啮齿动物中进行研究,而是需要在比较医学中进行研究,涉及大型、长寿的哺乳动物,以便为转化目的获得见解。