Alteration of striatal dopaminergic function induced by glioma development: a microdialysis and immunohistological study in the rat striatum

Tumoral growth effects on brain circuitry and neurochemical activities remain poorly documented. This study evaluates C6 graft effects on striatal dopaminergic afferent projections at both anatomical and functional levels. Immunohistochemistry was performed to investigate changes in neurofilament (NF), tyrosine hydroxylase (TH) and dopamine transporter (DAT) expression. Dopaminergic turnover was assessed using multiprobe microdialysis in freely-moving rat. In C6 graft striatum, dopamine (DA) catabolites were reduced in glioblastoma (DOPAC: -61%, HVA: -62%). In contrast, the DA level remained unchanged. Staining for NF, TH and DAT was drastically decreased inside the tumor. Our histological data report that striatal tumoral growth is associated with a decrease in the density of dopaminergic endings which can explain, at least in part, the decrease in DA turnover. The decrease in DAT transporter expression and the lack of change in DA level may result from an increase in DA diffusion from the peripheral areas of the tumor. In conclusion, glioblastoma growth has major consequences on the local neuronal circuitry and its neurochemistry. Changes in inter-connections and neurotransmitter turnover may result in abnormal neuronal firing activity and participate in clinical disorders associated with glioblastoma diagnosis.