Gómez-Pinilla Fernando, Ying Zhe, Roy Roland R, Hodgson John, Edgerton V Reggie
Department of Physiological Science, UCLA Brain Injury Research Center, Los Angeles, California 90095, USA.
J Neurophysiol. 2004 Dec;92(6):3423-32. doi: 10.1152/jn.00432.2004.
The effects of eliminating or decreasing neuromuscular activity on the expression of neurotrophins and associated molecules in the spinal cord and subsequent effects on spinal cord plasticity were determined. Spinal cord isolation (SI), which eliminates any supraspinal and peripheral monosynaptic input to the lumbar region but maintains the motoneuron-muscle connectivity, decreased the levels of brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) mRNA and protein in the isolated segments. Synapsin I, an important mediator for the effects of BDNF on synaptic plasticity, also was lower in the lumbar region of SI rats. In contrast, the levels of BDNF, synapsin, and growth-associated protein (GAP-43) were increased in the cervical spinal cord enlargement rostral to the isolated region, most likely reflecting an increased use of the forelimbs in the SI rats. GAP-43 levels were also increased in the lumbar spinal cord region, probably associated with compensatory mechanisms related to the deafferentation. In a separate set of experiments, the soleus muscle was paralyzed unilaterally via intramuscular botulinum toxin type A (BTX-A) injection to determine the effects of reducing the propioceptive input, of this normally highly active muscle on neurotrophin expression in the spinal cord. BDNF and synapsin I mRNAs were lower and NT-3 levels were higher in the lumbar hemicord ipsilateral to the BTX-A injection. Combined, these results indicate that the level of supraspinal and muscle afferent input plays an important role in modulating the levels of BDNF and NT-3 in the spinal cord.
确定了消除或降低神经肌肉活动对脊髓中神经营养因子及相关分子表达的影响，以及随后对脊髓可塑性的影响。脊髓隔离（SI）消除了对腰段的任何脊髓上和外周单突触输入，但维持了运动神经元与肌肉的连接，降低了隔离节段中脑源性神经营养因子（BDNF）和神经营养因子3（NT-3）的mRNA和蛋白质水平。突触素I是BDNF对突触可塑性作用的重要介质，在SI大鼠的腰段也较低。相比之下，在隔离区域头侧的颈脊髓膨大处，BDNF、突触素和生长相关蛋白（GAP-43）的水平升高，这很可能反映了SI大鼠前肢使用增加。腰段脊髓区域的GAP-43水平也升高，可能与去传入相关的代偿机制有关。在另一组实验中，通过肌内注射A型肉毒杆菌毒素（BTX-A）使比目鱼肌单侧麻痹，以确定减少这种正常高活性肌肉的本体感觉输入对脊髓中神经营养因子表达的影响。在注射BTX-A同侧的腰半脊髓中，BDNF和突触素I的mRNA较低，而NT-3水平较高。综合这些结果表明，脊髓上和肌肉传入输入水平在调节脊髓中BDNF和NT-3水平方面起着重要作用。
