Institute of Neuroscience, Department Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain.
Weill Institute for Neuroscience, Brain and Spinal Injury Center (BASIC), Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Exp Neurol. 2022 Dec;358:114220. doi: 10.1016/j.expneurol.2022.114220. Epub 2022 Sep 3.
Perineuronal nets (PNNs) are a specialized extracellular matrix that have been extensively studied in the brain. Cortical PNNs are implicated in synaptic stabilization, plasticity inhibition, neuroprotection, and ionic buffering. However, the role of spinal PNNs, mainly found around motoneurons, is still unclear. Thus, the goal of this study is to elucidate the role of spinal PNNs on motor function and plasticity in both intact and spinal cord injured mice. We used transgenic mice lacking the cartilage link protein 1 (Crtl1 KO mice), which is implicated in PNN assembly. Crtl1 KO mice showed disorganized PNNs with an altered proportion of their components in both motor cortex and spinal cord. Behavioral and electrophysiological tests revealed motor impairments and hyperexcitability of spinal reflexes in Crtl1 KO compared to WT mice. These functional outcomes were accompanied by an increase in excitatory synapses around spinal motoneurons. Moreover, following spinal lesions of the corticospinal tract, Crtl1 KO mice showed increased contralateral sprouting compared to WT mice. Altogether, the lack of Crtl1 generates aberrant PNNs that alter excitatory synapses and change the physiological properties of motoneurons, overall altering spinal circuits and producing motor impairment. This disorganization generates a permissive scenario for contralateral axons to sprout after injury.
周围神经毡（PNNs）是一种特殊的细胞外基质，在大脑中得到了广泛的研究。皮质 PNNs 参与突触稳定、可塑性抑制、神经保护和离子缓冲。然而，主要存在于运动神经元周围的脊髓 PNNs 的作用仍不清楚。因此，本研究的目的是阐明脊髓 PNNs 对正常和脊髓损伤小鼠运动功能和可塑性的作用。我们使用缺乏软骨连接蛋白 1（Crtl1 KO 小鼠）的转基因小鼠，该蛋白参与 PNN 的组装。Crtl1 KO 小鼠的 PNN 排列紊乱，其组成成分的比例在运动皮层和脊髓中都发生了改变。行为和电生理测试显示，与 WT 小鼠相比，Crtl1 KO 小鼠的运动功能受损，脊髓反射过度兴奋。这些功能结果伴随着脊髓运动神经元周围兴奋性突触的增加。此外，在皮质脊髓束损伤后，与 WT 小鼠相比，Crtl1 KO 小鼠的对侧发芽增加。总之，缺乏 Crtl1 会产生异常的 PNNs，改变兴奋性突触，改变运动神经元的生理特性，从而改变脊髓回路并导致运动功能障碍。这种紊乱为损伤后对侧轴突发芽创造了一个有利的环境。
