Jones S A, Holmes C, Budd T C, Greenfield S A
University Department of Pharmacology, Oxford, UK.
Cell Tissue Res. 1995 Feb;279(2):323-30. doi: 10.1007/BF00318488.
This study has investigated the possibility that acetylcholinesterase could play a non-classical role as an adhesion factor or growth factor in the development of dopaminergic neurons in organotypic slice culture of postnatal day 1 rats. When the culture medium was supplemented with acetylcholinesterase (3 U/ml), outgrowth of tyrosine hydroxylase-immunoreactive neurites was significantly enhanced. Addition of a specific inhibitor of acetylcholinesterase, BW284c51, caused a decrease in the number of tyrosine hydroxylase neurons and a reduction in the cell body size and extent of neurite outgrowth of remaining neurons. However, echothiophate which also inhibits AChE activity, did not produce these effects. Therefore acetylcholinesterase could act as a growth enhancing factor for dopaminergic neurons, and disruption of an as yet unidentified site on the acetylcholinesterase molecule by BW284c51 could decrease the survival and outgrowth of these neurons.
本研究探讨了乙酰胆碱酯酶在出生后第1天大鼠的器官型切片培养中作为多巴胺能神经元发育过程中的黏附因子或生长因子发挥非经典作用的可能性。当培养基中添加乙酰胆碱酯酶(3 U/ml)时,酪氨酸羟化酶免疫反应性神经突的生长显著增强。添加乙酰胆碱酯酶的特异性抑制剂BW284c51会导致酪氨酸羟化酶神经元数量减少,剩余神经元的细胞体大小和神经突生长范围减小。然而,同样抑制乙酰胆碱酯酶活性的依可碘酯并未产生这些影响。因此,乙酰胆碱酯酶可作为多巴胺能神经元的生长增强因子,而BW284c51对乙酰胆碱酯酶分子上一个尚未明确的位点的破坏可能会降低这些神经元的存活和生长。