Howells D W, Porritt M J, Wong J Y, Batchelor P E, Kalnins R, Hughes A J, Donnan G A
Department of Medicine, University of Melbourne, Heidelberg, Victoria, 3084, Australia.
Exp Neurol. 2000 Nov;166(1):127-35. doi: 10.1006/exnr.2000.7483.
Brain-derived neurotrophic factor (BDNF) has potent effects on survival and morphology of dopaminergic neurons and thus its loss could contribute to death of these cells in Parkinson's disease (PD). In situ hybridization revealed that BDNF mRNA is strongly expressed by dopaminergic neurons in control substantia nigra pars compacta (SNpc). In clinically and neuropathologically typical PD, SNpc BDNF mRNA expression is reduced by 70% (P = 0.001). This reduction is due, in part, to loss of dopaminergic neurons which express BDNF. However, surviving dopaminergic neurons in the PD SNpc also expressed less BDNF mRNA (20%, P = 0.02) than their normal counterparts. Moreover, while 15% of control neurons had BDNF mRNA expression >1 SD below the control mean, twice as many (28%) of the surviving PD SNpc dopaminergic neurons had BDNF mRNA expression below this value. This 13% difference in proportions (95% CI 8-17%, P < or = 0.000001) indicates the presence of a subset of neurons in PD with particularly low BDNF mRNA expression. Moreover, both control and PD neurons displayed a direct relationship between the density of BDNF mRNA expression per square micrometer of cell surface and neuronal size (r(2) = 0.93, P </= 0.00001) which was lost only in PD neurons expressing the lowest levels of BDNF mRNA. If BDNF is an autocrine/paracrine factor for SNpc dopaminergic neurons, loss of BDNF-expressing neurons may compromise the well-being of their surviving neighbors. Moreover, neurons expressing particularly low levels of BDNF mRNA may be those at greatest risk of injury in PD and possibly the trigger for the degeneration itself.
脑源性神经营养因子（BDNF）对多巴胺能神经元的存活和形态具有强大作用，因此其缺失可能导致帕金森病（PD）中这些细胞的死亡。原位杂交显示，在对照黑质致密部（SNpc）中，多巴胺能神经元强烈表达BDNF mRNA。在临床和神经病理学典型的PD中，SNpc的BDNF mRNA表达降低了70%（P = 0.001）。这种降低部分归因于表达BDNF的多巴胺能神经元的丧失。然而，PD的SNpc中存活的多巴胺能神经元表达的BDNF mRNA也比正常对应神经元少（20%，P = 0.02）。此外，虽然15%的对照神经元的BDNF mRNA表达低于对照平均值1个标准差，但存活的PD的SNpc多巴胺能神经元中，该比例是对照神经元的两倍（28%）。这13%的比例差异（95%置信区间8 - 17%，P≤0.000001）表明，PD中存在一部分BDNF mRNA表达特别低的神经元。此外，对照和PD神经元均显示，每平方微米细胞表面的BDNF mRNA表达密度与神经元大小之间存在直接关系（r² = 0.93，P≤0.00001），而这种关系仅在表达最低水平BDNF mRNA的PD神经元中丧失。如果BDNF是SNpc多巴胺能神经元的自分泌/旁分泌因子，表达BDNF的神经元的丧失可能会损害其存活邻居的健康。此外，表达特别低水平BDNF mRNA的神经元可能是PD中最易受损伤的神经元，也可能是变性本身的触发因素。
