脑源性神经营养因子基因敲除小鼠的小脑发育和叶形成异常揭示了神经营养因子在中枢神经系统模式形成中的作用。

Abnormal cerebellar development and foliation in BDNF-/- mice reveals a role for neurotrophins in CNS patterning.

作者信息

Schwartz P M, Borghesani P R, Levy R L, Pomeroy S L, Segal R A

机构信息

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Neuron. 1997 Aug;19(2):269-81. doi: 10.1016/s0896-6273(00)80938-1.

DOI:10.1016/s0896-6273(00)80938-1

PMID:9292718

Abstract

While target-derived neurotrophins are required for the survival of developing neurons in the PNS, the functions of neurotrophins in the CNS are unclear. Mice with a targeted gene deletion of brain-derived neurotrophic factor (BDNF) exhibit a wide-based gait. Consistent with this behavioral evidence of cerebellar dysfunction, there is increased death of granule cells, stunted growth of Purkinje cell dendrites, impaired formation of horizontal layers, and defects in the rostral-caudal foliation pattern. These abnormalities are accompanied by decreased Trk activation in granule and Purkinje cells of mutant animals, indicating that both cell types are direct targets for BDNF. These data suggest that BDNF acts as an anterograde or an autocrine-paracrine factor to regulate survival and morphologic differentiation of developing CNS neurons, and thereby affects neural patterning.

摘要

虽然靶源性神经营养因子是外周神经系统（PNS）中发育神经元存活所必需的，但神经营养因子在中枢神经系统（CNS）中的功能尚不清楚。脑源性神经营养因子（BDNF）基因靶向缺失的小鼠表现出宽基步态。与小脑功能障碍的这种行为证据一致的是，颗粒细胞死亡增加、浦肯野细胞树突生长受阻、水平层形成受损以及头尾叶状模式存在缺陷。这些异常伴随着突变动物颗粒细胞和浦肯野细胞中Trk激活的减少，表明这两种细胞类型都是BDNF的直接靶点。这些数据表明，BDNF作为一种顺行或自分泌-旁分泌因子，调节中枢神经系统发育中神经元的存活和形态分化，从而影响神经模式形成。