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Selective regional alterations in the content or distribution of neuronal and glial cytoskeletal proteins in brain of rats chronically exposed to 2,5-hexanedione

Laboratory of Neurobiology, Instituto de Investigaciones Citológicas, Fundación Valenciana de Investigaciones Biomedicas, Amadeo de Saboya, 4, 46010 Valencia, Spain

Regina Rodrigo

Laboratory of Neurobiology, Instituto de Investigaciones Citológicas, Fundación Valenciana de Investigaciones Biomedicas, Amadeo de Saboya, 4, 46010 Valencia, Spain

Vicente Felipo

Laboratory of Neurobiology, Instituto de Investigaciones Citológicas, Fundación Valenciana de Investigaciones Biomedicas, Amadeo de Saboya, 4, 46010 Valencia, Spain, vfelipo{at}ochoa.fib.es

Hexane is used in many industrial processes and induces neurotoxic effects in the central and peripheral nervous system. Hexane is metabolized to 2,5-hexanedione, which is the neurotoxic agent. Continued exposure to hexane or 2,5-hexanedione results in loss of sensorial and motor function in arms and legs and to alterations in axonal neurofilament proteins. The effects of 2,5-hexanedione on different cytoskeletal proteins in different brain areas have not been studied in detail. The aim of this work was to study the effects of chronic exposure of rats to 2,5-hexanedione (1% in the drinking water) on tubulin, neurofilament NF-L, microtubule-associated protein MAP-2, and on glial fibrillary acidic protein (GFAP), in cerebellum, hippocampus and cerebral cortex. The amount of each protein was determined by immunoblotting and its distribution was analysed by immunohistochemistry. The results obtained show a regional selectivity in the 2,5-hexanedione effects on cytoskeletal proteins. NF-L content decreased in all brain areas. MAP-2 decreased in cerebellum and hippocampus and tubulin decreased only in cerebellum. GFAP decreased only in cerebral cortex, but its distribution was altered in cerebellum, with increased content in the granular layer and decreased content in the molecular layer. The area most affected was the cerebellum, where all the proteins analysed were altered. These cytoskeletal proteins alterations may impair the transfer of information involved in the regulation by the cerebellum of motor function and contribute to the altered motor performance in rats exposed to 2,5-hexanedione and humans exposed to hexane.

Key Words: GFAP • 2,5-hexanedione • MAP-2 • neurofilament-L • neurotoxicity • tubulin

Toxicology and Industrial Health, Vol. 18, No. 7, 333-341 (2002)
DOI: 10.1191/0748233702th154oa


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