Acrylamide Neuropathy – I. Spatiotemporal Characteristics of Nerve Cell Damage in Rat Cerebellum

Abstract

Based on evidence from morphometric studies of PNS, we suggested that acrylamide (ACR)‐induced distal axon degeneration was a secondary effect related to duration of exposure (Toxicol Appl Pharmacol 151 [1998] 211). To test this hypothesis in CNS, the cupric‐silver stain method of de Olmos was used to define spatiotemporal characteristics of nerve somal, dendritic, axonal and terminal degeneration in rat cerebellum. Rats were exposed to ACR at either 50 mg/kg per day (i.p.) or 21 mg/kg per day (p.o.) and at selected times (i.p. = 5, 8 and 11 days; p.o. = 7, 14, 21, 28 and 38 days) brains were removed and processed for silver staining. Results demonstrate that intoxication at the higher ACR dose‐rate produced early (day 5) and progressive degeneration of Purkinje cell dendrites in cerebellar cortex. Nerve terminal degeneration occurred concurrently with somatodendritic argyrophilia in cerebellar and brainstent nuclei that receive afferent input from Purkinje neurons. Relatively delayed (day 8), abundant axon degeneration was present in cerebellar white matter but not in cortical layers or in tracts carrying afferent fibers (cerebellar peduncles) from other brain nuclei. Axon argyrophilia coincided with the appearance of perikaryal degeneration, which was selective for Purkinje cells since silver impregnation of other cerebellar neurons was not evident in the different cortical layers or cerebellar nuclei. Intoxication at the lower ACR dose‐rate produced simultaneous (day 14) dendrite, axon and nerve terminal argyrophilia and no somatic Purkinje cell degeneration. The spatiotemporal pattern of dendrite, axon and nerve terminal loss induced by both ACR dose‐rates is consistent with Purkinje cell injury. Injured neurons are likely to be incapable of maintaining, distal processes and, therefore, axon degeneration in the cerebellum is a component of a “dying‐back” process of neuronal injury. Because cerebellar coordination of somatomotor activity is mediated solely through efferent projections of the Purkinje cell, injury to this neuron might contribute significantly to gait abnormalities that characterize ACR neurotoxicity.

Hazardous effects of fried potato chips on the development of retina in albino rats

“…10-50 mg/kg per day for 28 days), axon degeneration in PNS and CNS occurred only during long-term exposure to lower ACR doserates (e.g. 21 mg/kg per day for 42 days) [6] . The dissociation between neurological dysfunction and the presumed underlying morphological lesion suggests that axonopathy might not be importantly involved in the pathophysiological process leading to ACR neurotoxicity.…”

“…Completed morphological studies [6] using a contemporary amino-cupric silver staining method to detect degenerating neurons and their processes indicated that intoxication at a higher ACR dose-rate produced selective, widespread degeneration of nerve terminals in rat brain and spinal cord regions. Intoxication at a lower dose rate was associated with initial nerve terminal degeneration followed later by pre-terminal axon degeneration.…”

“…It has been reported that ACR induced varieties of neurotoxicities [6][7][8] and it has been suggested that ACR manifested toxicity principally toward growth and development [9,10] . Moreover, ACR may affect the visual system in both animals [11,12] and humans [5] following absorption via dermal, oral or respiratory routes.…”

Protective Role of Kaempferol Against Acrylamide Intoxication

“…30,31 Evidences suggested that the neurotoxicity produced by A exposure is linked to nerve terminal damage in the central and peripheral nervous system which is mediated by injury to nerve terminals and cerebellar purkinje cells. 29,32 KPF is a natural poly phenol and have been established antioxidant effects in several studies.…”

Evaluation of <i>cII</i> gene mutation in the brains of Big Blue mice exposed to acrylamide and glycidamide in drinking water

“…*Statistically significant compared to corresponding control at p < 0.001. potential, AA is a known neurotoxin (Tilson, 1981) and several occupationally exposed population studies have been reported to have an increased incidence of neurotoxicity syndromes (Deng et al, 1993) with typical symptoms of ataxia, skeletal muscle weakness, and weight loss (LoPachin, 2005). Similarly, neurotoxicity has also been reported in animal studies of AA-exposure, and is largely characterized by sensory, autonomic, and motor deficits due to nerve terminal dysfunction in the thalamus, basal ganglia, and other regions of the brain (Lehning et al, 2003;LoPachin, 2004LoPachin, , 2005Mehri et al, 2015). Indeed, we observed symptoms that resembled hind limb paralysis and sluggishness at 3 weeks of exposure to the high dose of AA; however, the symptoms associated with the likely neurotoxicity disappeared after cessation of AA-treatment and animals returned to phenotypic normal as soon as the AA treatment was stopped.…”