Increased brain-derived neurotrophic factor-containing axons in the basal ganglia of patients with multiple system atrophy

Abstract

Brain-derived neurotrophic factor (BDNF) has a neurotrophic effect not only on mesencephalic dopaminergic neurons, but also on striatal neurons. To investigate whether the abnormal expression of BDNF occurs in the basal ganglia of patients with Parkinson disease (PD) and multiple system atrophy (MSA), we compared the BDNF levels in the striatum and globus pallidus of patients with PD or MSA to controls using immunohistochemistry. Furthermore, to quantitatively evaluate the immunohistochemical changes in the striatum, image analysis of the putamen was performed. BDNF positive nerve fiber bundles and fine granular structures were scattered throughout the striatum and globus pallidus of all samples. Most of these granular structures were observed in glial fibrillary acidic protein-positive astrocytes. In addition, BDNF-positive neurites were abundant in the striatum of all MSA patients, and numerous BDNF-positive varicose fibers were found in the globus pallidus of some MSA cases with particularly severe striatal involvement. These observations suggest that the upregulated expression of BDNF may occur as a protective mechanism in the striatum of MSA patients, and that severe striatal degeneration may cause the aberrant accumulation of BDNF in the striatal projection areas of the globus pallidus, of MSA patients.