A light and electron microscopic study of the effects of 3-acetylpyridine intoxication on the inferior olivary complex and cerebellar cortex.

The effects of 3-acetylpyridine (3-AP) intoxication on the inferior olivary complex and cerebellar cortex of the rat were examined at both the light and electron microscopic level. Following intraperitoneal injection of 65 mg of 3-AP per kg body weight, the inferior olivary neurons were observed to undergo a rapid form of electron dense degeneration. A complete bilateral involvement of the nuclear complex was well advanced as early as 12 hours following injection. Marked astrocytic proliferation also occurred by 12 hours and appeared essential for neuronal fragmentation and disintegration. Microglial activity was prominent in the later stages, from 60 hours onwards, and participated in the phagocytic removal of degenerating neuronal fragments. By the end of the second week, all cytoplasmic and nuclear debri was removed. Concurrently, degenerative changes in the cerebellar cortex were evident from 12 hours onwards. All climbing fiber varicosities were observed to be degenerative as early as 24 hours following treatment. Electron microscopic observations revealed that these electron dense fragments were largely phagocytized and cleared by Bergmann glial cells around 7 days. The sensitivity of the olivocerebellar system to 3-AP thus provides a convenient and selective means of eliminating all of the inferior olivary neurons and their axons, the climbing fibers of the cerebellar cortex. In contrast to the more conventionally used electrolytic methods, 3-AP causes a complete bilateral ablation of all olivary neurons while avoiding the problems inherent to electrolytic procedures, such as incomplete destruction of the nucleus and involvement of fibers of passage.