Reduced expression of brain-derived neurotrophic factor protein in Parkinson's disease substantia nigra

SEVERAL in vitro and in vivo studies have shown that brain-derived neurotro phic factor (BDNF) promotes survival of damaged mesencephalic dopaminergic neurons. Using a specific antibody directed against human recombinant BDNF, we studied the expression of the protein at the cellular level in the post -mortem mesencephalon of control subjects and patients with Parkinson's dis ease (PD). In control subjects, BDNF was expressed in all mesencephalic reg ions containing dopaminergic neurons, and in the substantia nigra pars comp acta (SNpc) 65% of the melanized neurons expressed BDNF. In the PD SNpc, th e total number of pigmented neurons containing BDNF was reduced to 9.6% of the corresponding control value. In contrast, the number of pigmented neuro ns non-immunoreactive for BDNF was reduced to 23.9% of the corresponding co ntrol value. This result appears to indicate that SNpc melanized neurons no t expressing BDNF have a 2.5-fold greater probability of surviving than BDN F-positive melanized neurons. Furthermore, we found that in parkinsonian me sencephalon almost all dopaminergic neurons containing Lewy bodies were imm unoreactive for BDNF. These findings demonstrate a reduced expression of BD NF in PD and suggest that BDNF protein expression does not protect melanize d SNpc neurons from the degenerative process in this disease. (C) 1999 Lipp incott Williams & Wilkins.