Ratnakumari L, Qureshi I A, Butterworth R F
Department of Medical Genetics, Hôpital Ste-Justine, Montreal, Que., Canada.
Neurosci Lett. 1994 Aug 29;178(1):63-5. doi: 10.1016/0304-3940(94)90290-9.
Congenital ornithine transcarbamylase (OTC) deficiency in humans is associated with seizures and mental retardation. As part of a series of studies to delineate the neurochemical features of OTC deficiency, activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), respectively, were measured in brain regions of the congenitally hyperammonemic sparse-fur (spf) mouse, a mutant with an X-linked inherited defect of OTC. ChAT activities were reduced by 63% (P < 0.01) in cerebral cortex of spf mice compared with CD-1/Y controls. Activities of the GABA nerve terminal marker enzyme, glutamic acid decarboxylase, on the other hand, were within normal limits. Using an immunohistochemical technique with a monoclonal antibody to ChAT, a significant loss of ChAT-positive neurons was observed throughout the cerebral cortex, septal area and diagonal band of spf mice. These results suggest that a loss of forebrain cholinergic neurons is a feature of congenital OTC deficiency in these mutants. Possible pathogenetic mechanisms responsible for the cholinergic neuronal loss in congenital OTC deficiency include neurotoxic effects of ammonia and accumulation of quinolinic acid.
人类先天性鸟氨酸转氨甲酰酶（OTC）缺乏与癫痫发作和智力发育迟缓有关。作为一系列描绘OTC缺乏神经化学特征研究的一部分，分别在先天性高氨血症稀毛（spf）小鼠（一种具有X连锁遗传OTC缺陷的突变体）的脑区中测量了胆碱乙酰转移酶（ChAT）和乙酰胆碱酯酶（AChE）的活性。与CD-1/Y对照相比，spf小鼠大脑皮质中的ChAT活性降低了63%（P < 0.01）。另一方面，GABA神经末梢标记酶谷氨酸脱羧酶的活性在正常范围内。使用针对ChAT的单克隆抗体的免疫组织化学技术，在spf小鼠的整个大脑皮质、隔区和斜角带观察到ChAT阳性神经元显著减少。这些结果表明，前脑胆碱能神经元的丧失是这些突变体先天性OTC缺乏的一个特征。先天性OTC缺乏中胆碱能神经元丧失的可能发病机制包括氨的神经毒性作用和喹啉酸的积累。
