Multidisciplinary morphological approaches to the intrinsic human cerebellar dopaminergic system, its projection and clinical role

Abstract

Introduction. Studies suggest that the cerebellum plays a role in dopaminergic disorders, such as Parkinson’s disease (PD) and Schizophrenia (SCZ). Data on an intrinsic human cere- bellar dopaminergic system and on a connection of the cerebellum with basal ganglia and the dopaminergic midbrain area are lacking. Studies demonstrate mainly in rodents an extrinsic dopaminergic fiber system in the cerebellum, originating from the A10 dopaminergic area, and few dopaminergic neurons composed by Purkinje neurons of the cerebellar cortex and by neu- rons of the deep cerebellar nuclei. Studies on the connection of the cerebellum with the brain area involved in PD and in SCZ are also lacking.

Aim. The aim of this study is to make an immunohistochemical investigation of the pres- ence of an intrinsic human cerebellar dopaminergic system. Recent developments in Diffusion Magnetic Resonance Tractography (DMRT) may allow in vivo studies of the cerebellar connec- tions with basal ganglia and the midbrain traditional dopaminergic area. Material and Meth- ods. Autoptic fragments of human cerebellum were fixed in an aldehyde picric acid solution, embedded in paraffin, cut into 5μm sections and subjected to light microscopic immunohisto- chemistry with rabbit polyclonal antibodies for dopamine transporter (DAT) or dopamine type 2 receptor (DRD2).

A 3T Achieva Philips scanner was used; a SENSE 8 channels head coil, acquiring T1 weight- ed 3D TFE, DTI sequences: data were analyzed using the contrastained spherical deconvolution technique (CDS). Results. DAT and DRD2 positivity was observed in the cerebellar cortex in Purkinje neurons, granules and in some non-traditional neuron types. In the dentate nucleus positivity was observed in large and small neuron types. We demonstrated with CSD cerebel- lar-subcortical connections. In particular, we found a direct route linking the dentate nucleus to the substantia nigra as well as to the ventro tegmental area.

Conclusions. This study demonstrates for the first time, the existence of an intrinsic human cerebellar dopaminergic system and a cortico-dentate and direct dentate nucleus connection with the substantia nigra and with the ventro tegmental area. Finally, we suggest that the cer- ebellum may be involved in dopaminergic brain disorders.