The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, 916 Hunterian Building, Baltimore, MD, USA.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, 916 Hunterian Building, Baltimore, MD, USA; Department of Neurobiology and Anatomy, University of Utah, School of Medicine, 20 South 2030 East, Room 320 BPRB, Salt Lake City, UT, USA.
Exp Neurol. 2020 Jan;323:113089. doi: 10.1016/j.expneurol.2019.113089. Epub 2019 Nov 4.
Serotonin axons in the adult rodent brain can regrow and recover their function following several forms of injury including controlled cortical impact (CCI), a neocortical stab wound, or systemic amphetamine toxicity. To assess whether this capacity for regrowth is unique to serotonergic fibers, we used CCI and stab injury models to assess whether fibers from other neuromodulatory systems can also regrow following injury. Using tyrosine-hydoxylase (TH) immunohistochemistry we measured the density of catecholaminergic axons before and at various time points after injury. One week after CCI injury we observed a pronounced loss, across cortical layers, of TH+ axons posterior to the site of injury. One month after CCI injury the same was true of TH+ axons both anterior and posterior to the site of injury. This loss was followed by significant recovery of TH+ fiber density across cortical layers, both anterior and posterior to the site of injury, measured three months after injury. TH+ axon loss and recovery over weeks to months was also observed throughout cortical layers using the stab injury model. Double label immunohistochemistry revealed that nearly all TH+ axons in neocortical layer 1/2 are also dopamine-beta-hyroxylase+ (DBH+; presumed norepinephrine), while TH+ axons in layer 5 are a mixture of DBH+ and dopamine transporter+ types. This suggests that noradrenergic axons can regrow following CCI or stab injury in the adult mouse neocortex and leaves open the question of whether dopaminergic axons can do the same.
成年啮齿动物大脑中的 5-羟色胺轴突在多种形式的损伤后可以再生并恢复功能，包括控制性皮质撞击（CCI）、新皮层刺伤或全身安非他命毒性。为了评估这种再生能力是否是 5-羟色胺能纤维所特有的，我们使用 CCI 和刺伤损伤模型来评估其他神经调质系统的纤维在损伤后是否也能再生。我们使用酪氨酸羟化酶（TH）免疫组织化学方法测量损伤前后不同时间点的儿茶酚胺能轴突密度。CCI 损伤后 1 周，我们观察到损伤部位后部皮质各层 TH+轴突明显丢失。CCI 损伤后 1 个月，损伤部位前后的 TH+轴突也是如此。在损伤后 3 个月，皮质各层 TH+纤维密度均显著恢复。在刺伤损伤模型中，我们还观察到在数周到数月的时间内，TH+轴突丢失和恢复遍及整个皮质层。双重免疫组织化学显示，新皮层 1/2 层中几乎所有的 TH+轴突也是多巴胺-β-羟化酶+（DBH+；假定去甲肾上腺素），而 5 层中的 TH+轴突是 DBH+和多巴胺转运体+类型的混合物。这表明去甲肾上腺素能轴突可以在成年小鼠新皮层的 CCI 或刺伤后再生，并且开放性问题是多巴胺能轴突是否也可以这样做。
