Reduced BDNF mRNA expression in the Parkinson's disease substantia nigra

Brain-derived neurotrophic factor (BDNF) has potent effects on survival and morphology of dopaminergic neurons and thus its loss could contribute to d eath of these cells in Parkinson's disease (PD). In situ hybridization reve aled that BDNF mRNA is strongly expressed by dopaminergic neurons in contro l substantia nigra pars compacts (SNpc). In clinically and neuropathologica lly typical PD, SNpc BDNF mRNA expression is reduced by 70% (P = 0.001). Th is reduction is due, in part, to loss of dopaminergic neurons which express BDNF. However, surviving dopaminergic neurons in the PD SNpc also expresse d less BDNF mRNA (20%, P = 0.02) than their normal counterparts. Moreover, while 15% of control neurons had BDNF mRNA expression >1 SD below the contr ol mean, twice as many (28%) of the surviving PD SNpc dopaminergic neurons had BDNF mRNA expression below this value. This 13% difference in proportio ns (95% CI 8-17%, P less than or equal to 0.000001) indicates the presence of a subset of neurons in PD with particularly low BDNF mRNA expression. Mo reover, both control and PD neurons displayed a direct relationship between the density of BDNF mRNA expression per square micrometer of cell surface and neuronal size (r(2) = 0.93, P less than or equal to 0.00001) which was lost only in PD neurons expressing the lowest levels of BDNF mRNA. If BDNF is an autocrine/ paracrine factor for SNpc dopaminergic neurons, loss of BD NF-expressing neurons may compromise the well-being of their surviving neig hbors. Moreover, neurons expressing particularly low levels of BDNF mRNA ma y be those at greatest risk of injury in PD and possibly the trigger for th e degeneration itself. (C) 2000 Academic Press.