Yasuhara T, Hara K, Maki M, Matsukawa N, Fujino H, Date I, Borlongan C V
Department of Neurology, Medical College of Georgia, Augusta, GA USA.
Neuroscience. 2007 Oct 12;149(1):182-91. doi: 10.1016/j.neuroscience.2007.07.045. Epub 2007 Aug 9.
Bedridden patients who receive good physical rehabilitation are able to exhibit clinical improvement. Accumulating evidence demonstrates that exercise increases endogenous neurogenesis and may even protect against central nervous system (CNS) disorders. Here, we explored the effects of lack of exercise on neurogenesis in rats by employing a routine hindlimb suspension (HS) model over a 2-week period, which consists of elevating their tails, thereby raising their hindlimbs above the ground and unloading the weights in these extremities. In addition, the effects of exercise and recovery time with normal caging after HS were also explored. BrdU (50 mg/kg, i.p.) was injected every 8 h over the last 4 days of each paradigm to label proliferative cells. Immunohistochemical results revealed that HS significantly reduced the number of BrdU/Doublecortin double-positive cells in the subventricular zone and dentate gyrus. Exercise and recovery time significantly improved atrophy of the soleus muscle, but did not attenuate the HS-induced decrement in BrdU/Dcx-positive cells. A separate cohort of animals was exposed to the same HS paradigm and enzyme-linked immunosorbent assay (ELISA) of neurotrophic factors was performed on brain tissue samples harvested at the end of the HS period, as well as plasma samples from all animals. ELISA results revealed that HS reduced the levels of brain-derived neurotrophic factor in the hippocampus and vascular endothelial growth factor plasma levels. This study revealed that lack of exercise reduced neurogenesis with downregulation of neurotrophic factors. The use of the HS model in conjunction with CNS disease models should further elucidate the role of exercise in neurogenesis and neurotrophic factors in neurologic disorders.
接受良好身体康复治疗的卧床患者能够表现出临床改善。越来越多的证据表明，运动可增加内源性神经发生，甚至可能预防中枢神经系统（CNS）疾病。在此，我们通过采用常规后肢悬吊（HS）模型，在为期2周的时间内探究了运动缺乏对大鼠神经发生的影响，该模型包括抬高大鼠尾巴，从而使其后肢高于地面并卸载这些肢体的重量。此外，还探究了HS后运动及恢复正常笼养时间的影响。在每个实验范式的最后4天，每8小时腹腔注射一次BrdU（50mg/kg）以标记增殖细胞。免疫组织化学结果显示，HS显著减少了脑室下区和齿状回中BrdU/双皮质素双阳性细胞的数量。运动和恢复时间显著改善了比目鱼肌萎缩，但并未减轻HS诱导的BrdU/Dcx阳性细胞数量减少。另一组动物接受相同的HS范式，并在HS期结束时采集的脑组织样本以及所有动物的血浆样本上进行神经营养因子的酶联免疫吸附测定（ELISA）。ELISA结果显示，HS降低了海马中脑源性神经营养因子水平以及血浆中血管内皮生长因子水平。本研究表明，运动缺乏通过下调神经营养因子减少了神经发生。将HS模型与CNS疾病模型结合使用应能进一步阐明运动在神经发生中的作用以及神经营养因子在神经系统疾病中的作用。
