Deller Thomas, Del Turco Domenico, Rappert Angelika, Bechmann Ingo
Institute of Clinical Neuroanatomy, J.W. Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
Prog Brain Res. 2007;163:501-28. doi: 10.1016/S0079-6123(07)63027-1.
Deafferentation of the dentate gyrus by unilateral entorhinal cortex lesion or unilateral perforant pathway transection is a classical model to study the response of the central nervous system (CNS) to denervation. This model has been extensively characterized in the rat to clarify mechanisms underlying denervation-induced gliosis, transneuronal degeneration of denervated neurons, and collateral sprouting of surviving axons. As a result, candidate molecules have been identified which could regulate these changes, but a causal link between these molecules and the postlesional changes has not yet been demonstrated. To this end, mutant mice are currently studied by many groups. A tacit assumption is that data from the rat can be generalized to the mouse, and fundamental species differences in hippocampal architecture and the fiber systems involved in sprouting are often ignored. In this review, we will (1) provide an overview of some of the basics and technical aspects of the entorhinal denervation model, (2) identify anatomical species differences between rats and mice and will point out their relevance for the axonal reorganization process, (3) describe glial and local inflammatory changes, (4) consider transneuronal changes of denervated dentate neurons and the potential role of reactive glia in this context, and (5) summarize the differences in the reorganization of the dentate gyrus between the two species. Finally, we will discuss the use of the entorhinal denervation model in mutant mice.
通过单侧内嗅皮层损伤或单侧穿通通路横断造成齿状回传入神经阻滞是研究中枢神经系统（CNS）对去神经支配反应的经典模型。该模型在大鼠中已得到广泛研究，以阐明去神经支配诱导的胶质增生、去神经支配神经元的跨神经元变性以及存活轴突的侧支发芽的潜在机制。因此，已鉴定出可能调节这些变化的候选分子，但这些分子与损伤后变化之间的因果关系尚未得到证实。为此，目前许多研究小组正在研究突变小鼠。一个默认的假设是，大鼠的数据可以推广到小鼠，而海马结构和参与发芽的纤维系统的基本物种差异常常被忽视。在这篇综述中，我们将：（1）概述内嗅去神经支配模型的一些基础知识和技术方面；（2）确定大鼠和小鼠之间的解剖学物种差异，并指出它们与轴突重组过程的相关性；（3）描述胶质细胞和局部炎症变化；（4）考虑去神经支配的齿状神经元的跨神经元变化以及反应性胶质细胞在此过程中的潜在作用；（5）总结两个物种在齿状回重组方面的差异。最后，我们将讨论内嗅去神经支配模型在突变小鼠中的应用。
