Hyde G E, Durham D
Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle 98195.
J Comp Neurol. 1994 Jan 1;339(1):27-48. doi: 10.1002/cne.903390105.
Second-order auditory neurons in nucleus magnocellularis (NM) of the chick brainstem undergo a series of rapid metabolic changes following unilateral cochlea removal, culminating in the death of 25% of NM neurons. Within hours of cochlea removal, ipsilateral NM neurons show marked increases in histochemical staining for the mitochondrial enzymes succinate dehydrogenase and cytochrome oxidase. We investigated corresponding ultrastructural changes in NM neurons by preparing animals undergoing unilateral cochlea removal for transmission electron microscopy. We quantified changes in NM mitochondrial volume by stereological methods and qualitatively compared mitochondrial morphology between NM neurons destined to survive and those destined to die after cochlea removal. Within hours of cochlea removal, ipsilateral NM neurons show striking increases in mitochondrial volume (84% at 6 hours and 236% at 12 hours after cochlea removal compared to unoperated, control animals). At 2 week survival times, ipsilateral NM neurons contain fewer mitochondria than contralateral neurons. Surprisingly, anesthesia alone causes short-term increases in NM mitochondrial volume. Animals anesthetized with pentobarbital and ketamine and sacrificed 6 or 12 hours later showed a 45% increase in mitochondrial volume compared to previously unanesthetized animals. NM neurons destined to die within days of cochlea removal can be identified within several hours after deafferentation by the appearance of their ribosomes. We observed qualitative differences in mitochondrial morphology in dying neurons. Mitochondria in neurons destined to die consistently showed mitochondrial swelling and vacuolization indicative of metabolic dysfunction. Similar mitochondrial changes have been reported when mitochondria take up excess calcium. Ultrastructural changes in NM after cochlea removal display features of both programmed and pathological cell death, in which increased intracellular calcium is thought to play a role.
雏鸡脑干大细胞神经核（NM）中的二级听觉神经元在单侧耳蜗切除后会经历一系列快速的代谢变化，最终导致25%的NM神经元死亡。在耳蜗切除后的数小时内，同侧NM神经元的线粒体酶琥珀酸脱氢酶和细胞色素氧化酶的组织化学染色显著增加。我们通过制备单侧耳蜗切除的动物进行透射电子显微镜检查，研究了NM神经元相应的超微结构变化。我们采用体视学方法量化了NM线粒体体积的变化，并定性比较了耳蜗切除后注定存活和注定死亡的NM神经元之间的线粒体形态。在耳蜗切除后的数小时内，同侧NM神经元的线粒体体积显著增加（与未手术的对照动物相比，耳蜗切除后6小时增加84%，12小时增加236%）。在存活2周时，同侧NM神经元的线粒体比 contralateral神经元少。令人惊讶的是，仅麻醉就会导致NM线粒体体积短期增加。用戊巴比妥和氯胺酮麻醉并在6或12小时后处死的动物，其线粒体体积比先前未麻醉的动物增加了45%。在耳蜗切除后数天内注定死亡的NM神经元在去传入神经后数小时内可通过核糖体的出现来识别。我们观察到垂死神经元中线粒体形态的质的差异。注定死亡的神经元中的线粒体持续显示出线粒体肿胀和空泡化，这表明代谢功能障碍。当线粒体摄取过量钙时，也有类似的线粒体变化报道。耳蜗切除后NM的超微结构变化显示出程序性细胞死亡和病理性细胞死亡的特征，其中细胞内钙增加被认为起了作用。
