DOES THE CALCIUM-BINDING PROTEIN CALRETININ PROTECT DOPAMINERGIC-NEURONS AGAINST DEGENERATION IN PARKINSONS-DISEASE

Parkinson's disease (PD) is characterized by a heterogeneous loss of d opaminergic neurons in the human mesencephalon affecting mainly the su bstantia nigra pars compacta (SNpc) and to a lesser extent the other d opaminergic cell groups. A rise in intracellular calcium concentration s represents one of the final events leading to nerve cell death. Calb indin D28k, a protein capable of buffering intracellular calcium conce ntrations is present in the dopaminergic neurons that are selectively preserved in PD but not in those that degenerate. To determine whether other calcium-binding proteins also represent putative protective fac tors of dopaminergic neurons in PD, we analyzed immunohistochemically the distribution of calretinin-containing (CR(+)) neurons, in the huma n mesencephalon of three control subjects and four patients with PD. N o significant differences were observed between the number of CR(+) ne urons in the two subject groups. Sequential double immunostaining for calretinin and tyrosine hydroxylase showed a variable proportion of CR (+) neurons among dopaminergic neurons: moderate co-localization was f ound in catecholaminergic cell group As and in the dorsal part of the Ventral tegmental area (VTA) and low co-localization in the SNpc, the ventral part of the VTA and the central gray substance. This indicates that calretinin may only protect some dopaminergic neurons against de generation in PD. Yet, in the SNpc a selective preservation of CR(+) d opaminergic neurons was observed, suggesting a neuroprotective role in some dopaminergic cell groups only.