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用α-氨基-3-羟基-4-异恶唑丙酸(AMPA)单侧损毁大鼠基底核后,大鼠大脑皮质胆碱能神经支配的可塑性变化:前脑基底移植入新皮质的影响。

Plastic changes in the cholinergic innervation of the rat cerebral cortex after unilateral lesion of the nucleus basalis with alpha-amino-3-OH-4-isoxozole propionic acid (AMPA): effects of basal forebrain transplants into neocortex.

作者信息

Calaminici M, Abdulla F A, Sinden J D, Stephenson J D

机构信息

Department of Neuroscience, Institute of Psychiatry, London, UK.

出版信息

Brain Res Bull. 1997;42(2):79-93. doi: 10.1016/s0361-9230(96)00212-2.

DOI:10.1016/s0361-9230(96)00212-2
PMID:8971411
Abstract

Unilateral AMPA lesions of the nucleus basalis magnocellularis (nbm) produced a nearly complete loss of cholinergic markers in the ipsilateral frontal and parietal cortices with no recovery at 6 months. The loss was associated with compensatory increases in AChE-positive fibre density in the contralateral cortex, in ipsilateral cortical regions not receiving their cholinergic innervation from the nbm and in the size of cholinergic magnocellular neurones in the contralateral nbm. The hypertrophy and increase in AChE-positive fibre density were apparent at 4-6 weeks after lesion and increased with time. Cholinergic transplants to cholinergically deafferented cortex prevented development of the compensatory increases in AChE-positive fibre density and restored AChE-positive fibre density and ChAT activity to control levels in ipsilateral cholinergically deafferented regions, partially after 6-8 weeks and completely after 6 months. In contrast, when cholinergic grafts were placed into unlesioned cortex, axonal outgrowth was localized to the vicinity of the transplant and did not develop with time. These results support the concept that vacant synapses promote and direct axonal outgrowth from transplanted neurones and that grafted cholinergic neurones integrate into the lesioned forebrain cholinergic projections system and prevent the lesion-induced changes in AChE-positive fibre density and ChAT activity.

摘要

基底大细胞核(nbm)的单侧AMPA损伤导致同侧额叶和顶叶皮质中胆碱能标志物几乎完全丧失,6个月时无恢复。这种丧失与对侧皮质、未接受来自nbm胆碱能神经支配的同侧皮质区域以及对侧nbm中胆碱能大细胞神经元大小的AChE阳性纤维密度的代偿性增加有关。损伤后4 - 6周,肥大和AChE阳性纤维密度增加明显,并随时间增加。向胆碱能去传入皮质移植胆碱能神经元可防止AChE阳性纤维密度代偿性增加的发展,并使同侧胆碱能去传入区域的AChE阳性纤维密度和ChAT活性恢复到对照水平,6 - 8周后部分恢复,6个月后完全恢复。相反,当将胆碱能移植物置于未损伤的皮质时,轴突生长局限于移植物附近,且不会随时间发展。这些结果支持这样的概念,即空突触促进并引导移植神经元的轴突生长,并且移植的胆碱能神经元整合到损伤的前脑胆碱能投射系统中,并防止损伤诱导的AChE阳性纤维密度和ChAT活性变化。

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