Brain-derived neurotrophic factor in Huntington disease

Trophic factors, administered systemically or delivered via genetically-mod ified cells grafted into target regions, have been proposed as putative the rapeutic agents in human neurodegenerative disorders. In parallel to the st udy of the beneficial effects in experimental models of particular diseases , a crucial aspect of the study of trophic factors is the gathering of info rmation about the actual trophic factor expression in human diseased states . Brain-derived neurotrophic factor (BDNF) promotes survival and growth of various nerve cell populations during normal development and following vari ous insults in the developing and adult brain. In particular, BDNF prevents cell death of certain striatal populations in excitotoxic models of Huntin gton disease (HD) following intrastriatal injection of quinolinic acid to t he adult rodent brain. The present study examines BDNF expression, by gel e lectrophoresis and Western blotting, and immunohistochemistry, in the brain s of patients who had suffered from HD. Reduced BDNF expression, ranging fr om 53 to 82%, has been found in the caudate and putamen in HD when compared with age-matched controls. No modifications in BDNF expression levels have been seen in the parietal cortex, temporal cortex and hippocampus. Further more, immunohistochemistry has shown reduced BDNF immunoreactivity in cauda te neurons, but not in cortical neurons in HD when compared with controls. These data demonstrate selective BDNF decay in regions that are vulnerable to HD, and suggest, in combination with results in experimental models, tha t a BDNF surplus may have beneficial effects in the treatment of HD. (C) 20 00 Elsevier Science B.V. All rights reserved.