Rodríguez-Ithurralde D, Olivera S, Migues V, Vincent O, Salazar R
Laboratory of Molecular Neuroscience, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay.
J Neurol Sci. 1995 May;129 Suppl:104-6. doi: 10.1016/0022-510x(95)00077-f.
To investigate the mechanisms by which glutamate-induced acetylcholinesterase (AChE) release might play a part in the pathogenesis of excitotoxically triggered motor neurone disease, we measured AChE molecular forms released after glutamate-receptor agonist stimulation of superfused and incubated slices of mouse spinal cord. Kainate and GLU caused a dose-related, calcium-dependent, magnesium-blocked liberation of AChE soluble forms (mainly G4) from both the ventral and dorsal horns, without membrane damage. In the immature slice, glycine potentiated GLU elicited AChE release in the presence of strychnine, suggesting N-methyl-D-aspartate (NMDA) receptor involvement. After the 30th postnatal day, nearly all the release was caused by non-NMDA receptor stimulation. The response might interfere with the negative feedback loop which modulates the overactivation of motor neurones, and might render them more vulnerable to excitotoxic stress.
为了研究谷氨酸诱导的乙酰胆碱酯酶（AChE）释放可能在兴奋性毒性触发的运动神经元疾病发病机制中发挥作用的机制，我们测量了谷氨酸受体激动剂刺激小鼠脊髓灌流和孵育切片后释放的AChE分子形式。海人酸和谷氨酸引起剂量相关、钙依赖性、镁阻断的AChE可溶性形式（主要是G4）从腹角和背角的释放，且无膜损伤。在未成熟切片中，甘氨酸增强谷氨酸在士的宁存在下引起的AChE释放，提示N-甲基-D-天冬氨酸（NMDA）受体参与。出生后第30天之后，几乎所有释放都是由非NMDA受体刺激引起的。这种反应可能会干扰调节运动神经元过度激活的负反馈回路，并可能使它们更容易受到兴奋性毒性应激的影响。
