3‐Acetylpyridine‐induced degeneration in the dorsal root ganglia: involvement of small diameter neurons and influence of axotomy

Abstract

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.

Transitory disappearance of microglia during the regeneration of the lizard medial cortex

“…As the loss of energy kills the neurons, they become swollen due to passive water intake after failure of the ATPase Na/K pump. The edema, the disrupted morphology of the cytoplasm displayed by afTected neuronal somata, and, finally, the delayed presence of debris all suggest a necrotic process in the lesioned medial cortex (Auer et al, 1985;Beiswanger et al, 1993).…”

Vacuolation of Sensory Ganglion Neuron Cytoplasm in Rats with Long-term Exposure to Organophosphates

“…Chemotherapeutic agents, such as paclitaxel, cisplatin (Melli et al 2008), and bortezomib (Cavaletti et al 2007) have been shown to induce numerous small neuronal, cytoplasmic vacuoles that originate from damaged mitochondria. Similarly, after exposures to toxicants like 3-acetylpyramide (Beiswanger et al 1993) and acrylamide (Groves and Scaravilli 2005; Lehning et al 1998; Schaumberg and Berger 1993), sensory neurons have been reported to develop many small vacuoles as a result of inhibition of NAD/NADP-dependent pathways and decreased Na/K-ATPase activity, respectively. These vacuoles differ from the large vacuoles we report.…”

“…Cytoplasmic vacuolation of sensory neurons is a striking finding that has been reported to occur in the dorsal root ganglia following exposure to several toxic agents (Beiswanger et al 1993; Cavaletti et al 2007; Jaatinen et al 1994; Melli et al 2008), and in diabetes mellitus (Kamiya et al 2006), traumatic axonal injury (Groves et al 1997), and aging (Groves and Scaravilli 2005). They also have been seen at very low incidences in normal animals (Groves and Scaravilli 2005).…”