Identification of CB2 receptors in human nigral neurons that degenerate in Parkinson's disease

It is well-demonstrated that cannabinoid CB2 receptors located in glial cells are up-regulated in neurodegenerative disorders serving as a target to control glial influences to neurons. Recent evidence indicates that CB2 receptors may be also located in certain neuronal subpopulations and serve as a marker of neuronal losses. We investigated this possibility in the post-mortem substantia nigra of Parkinson's disease (PD) patients and controls. Immunostaining for the CB2 receptor was found in tyrosine hydroxylase-positive neurons in the substantia nigra, a fact confirmed with double-staining analyses. The signal was found in controls but also in PD patients, in which CB2 receptor labelling was significantly lower, in parallel to the losses of these neurons experienced in the disease. These data show for the first time that CB2 receptors are located in tyrosine hydroxylase-containing neurons in the substantia nigra at levels significantly lower in PD patients compared to controls.