Pettigrew D B, Crutcher K A
Dept. of Neurobiology and Anatomy University of Texas-Houston Health Science Center, USA.
BMC Neurosci. 2001;2:9. doi: 10.1186/1471-2202-2-9. Epub 2001 May 31.
Brain and spinal cord white matter can support extensive axonal growth. This growth is generally constrained to an orientation that is parallel to the longitudinal axis of the fiber tract. This constraint is presumably due to permissive and non-permissive substrates that are interleaved with each other and oriented in parallel within the tract.
Embryonic chick sympathetic neurons were cultured on cryostat sections of rat brain and the orientation of neurite growth on white matter was assessed. To determine if haptotaxis is sufficient to guide parallel neurite growth, neurons were cultured under conditions designed to interfere with interactions between growing neurites and factors that act as biochemical contact guidance cues but not interactions with haptotactic cues. Under these conditions, neurites extending on white matter were not exclusively oriented in parallel to the fiber tract, suggesting that biochemical cues are involved. To assess the role of myelin in guiding parallel neurite growth, neurons were cultured on myelin-deficient corpus callosum. These neurons also extended neurites that were not constrained to a parallel orientation. Moreover, preincubation with NGF and treatment with cAMP analogs, manipulations that attenuate overall myelin-mediated inhibition of neurite growth, also led to a reduced parallel orientation of neurite growth.
The present studies suggest that some of the relevant factors that constrain axonal growth on white matter are not haptotactic in nature and appear to be partly mediated by factors that are associated with myelin and may involve myelin-associated "inhibitors".
脑和脊髓白质能够支持广泛的轴突生长。这种生长通常局限于与纤维束纵轴平行的方向。这种限制可能是由于相互交错且在纤维束内平行排列的允许性和非允许性底物所致。
将胚胎期鸡交感神经元培养在大鼠脑的冰冻切片上，并评估白质上神经突生长的方向。为了确定趋触性是否足以引导平行的神经突生长，在旨在干扰生长中的神经突与作为生化接触导向线索的因子之间的相互作用但不干扰与趋触性线索相互作用的条件下培养神经元。在这些条件下，在白质上延伸的神经突并非完全与纤维束平行排列，这表明生化线索参与其中。为了评估髓磷脂在引导平行神经突生长中的作用，将神经元培养在髓磷脂缺陷的胼胝体上。这些神经元也延伸出不受平行方向限制的神经突。此外，用神经生长因子预孵育并用环磷酸腺苷类似物处理，这些操作减弱了髓磷脂对神经突生长的总体抑制作用，也导致神经突生长的平行方向减少。
目前的研究表明限制白质上轴突生长的一些相关因素本质上不是趋触性的，似乎部分由与髓磷脂相关的因子介导，并且可能涉及髓磷脂相关的“抑制剂”。
