Batchelor P E, Liberatore G T, Porritt M J, Donnan G A, Howells D W
Department of Medicine, University of Melbourne, Austin, Australia.
Eur J Neurosci. 2000 Oct;12(10):3462-8. doi: 10.1046/j.1460-9568.2000.00239.x.
After striatal injury, sprouting dopaminergic fibres grow towards and intimately surround wound macrophages which, together with microglia, express the dopaminergic neurotrophic factors glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF). To evaluate the importance of these endogenously secreted neurotrophic factors in generating striatal peri-wound dopaminergic sprouting, the peri-wound expression of BDNF or GDNF was inhibited by intrastriatal infusion of antisense oligonucleotides for 2 weeks in mice. Knock-down of both BDNF and GDNF mRNA and protein levels in the wounded striatum were confirmed by in situ hybridization and enzyme-linked immunosorbent assay, respectively. Dopamine transporter immunohisto-chemistry revealed that inhibition of either BDNF or GDNF expression resulted in a marked decrease in the intensity of peri-wound sprouting. Quantification of this effect using [H3]-mazindol autoradiography confirmed that peri-wound sprouting was significantly reduced in mice receiving BDNF or GDNF antisense infusions whilst control infusions of buffered saline or sense oligonucleotides resulted in the pronounced peri-wound sprouting response normally associated with striatal injury. BDNF and GDNF thus appear to be important neurotrophic factors inducing dopaminergic sprouting after striatal injury.
纹状体损伤后，新生的多巴胺能纤维向伤口巨噬细胞生长并紧密围绕它们，这些巨噬细胞与小胶质细胞一起表达多巴胺能神经营养因子，即胶质细胞源性神经营养因子（GDNF）和脑源性神经营养因子（BDNF）。为了评估这些内源性分泌的神经营养因子在纹状体伤口周围多巴胺能纤维新生中的重要性，通过向小鼠纹状体内注射反义寡核苷酸2周来抑制BDNF或GDNF在伤口周围的表达。分别通过原位杂交和酶联免疫吸附测定证实了受伤纹状体中BDNF和GDNF的mRNA及蛋白水平的下调。多巴胺转运体免疫组化显示，抑制BDNF或GDNF的表达会导致伤口周围纤维新生强度显著降低。使用[H3]-马吲哚放射自显影对这种效应进行定量分析，结果证实，接受BDNF或GDNF反义寡核苷酸注射的小鼠伤口周围纤维新生明显减少，而注射缓冲盐水或正义寡核苷酸的对照小鼠则出现了通常与纹状体损伤相关的明显的伤口周围纤维新生反应。因此，BDNF和GDNF似乎是纹状体损伤后诱导多巴胺能纤维新生的重要神经营养因子。
