05-11-2003, 07:05 AM
• Lehning EJ, Balaban CD, Ross JF, Reid MA and LoPachin RM (2002). Acrylamide neuropathy. I. Spatiotemporal characteristics of nerve cell damage in rat cerebellum. Neurotoxicology 23:397-414. Summary: 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 brainstem 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. Department of Anesthesiology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA.