3-Acetylpyridine-induced degeneration in the dorsal root ganglia: involvement of small diameter neurons and influence of axotomy.
3-Acetylpyridine (3-AP), an analogue of nicotinamide, produces highly selective CNS lesions, the severity of which may be influenced by prior alterations in the metabolic activity of the affected neurons. The present study was undertaken to determine whether prior axotomy modified the response of dorsal root ganglia (DRG) and anterior horn (AH) neurons to 3-AP. A single administration (50 or 80 mg/kg i.p.) of 3-AP to adult rats resulted in degeneration of primarily small-dark DRG neurons by 24 h. The AH neurons were not affected by either dose of 3-AP. Light and electron microscopy of the DRG revealed a spectrum of damage ranging from loss of Nissl substance and cytoplasmic degradation to frank necrosis with neuronophagia. Frequently, injured neurons exhibited perinuclear aggregation of cytoplasmic organelles with dissolution of Nissl substance, clearing of the peripheral cytoplasm, and formation of large peripheral vacuoles. Occasionally, a second pattern of 3-AP injury was observed in which the nuclear chromatin of the neurons was condensed and there was formation of small vacuoles throughout the cytoplasm without peripheral clearing or perinuclear aggregation of cytoplasmic organelles. Axotomy induced typical axon reactions in both large-pale and small-dark DRG neurons. The combination of axotomy followed by 3-AP 4 days later produced morphological features characteristic of both axotomy and 3-AP exposure, but did not appear to alter the incidence of neuronal cell death. The almost exclusive vulnerability of the small dorsal root ganglion neurons to 3-AP neurotoxicity make this model potentially useful for the study of small fibre neuropathies.
Beiswanger
C M
CM
Department of Pharmacology and Toxicology, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08855.
Roscoe-Graessle
T L
TL
Zerbe
N
N
Reuhl
K R
KR
Lowndes
H E
HE
D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002843:Chromatin / Q000648:ultrastructure; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology*; D009410:Nerve Degeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D011725:Pyridines / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology
D002843:Chromatin; D011725:Pyridines; C010835:3-acetylpyridine