Molecular and morphological analysis of the dopaminergic neurons in human substantia nigra : new citopathological findings in Parkinson's disease

Parkinson's disease (PD) is the most common movement disorder and the second chronic progressive neurodegenerative disease. Fragmentation of the Golgi ribbon is a common feature of many neurodegenerative diseases, including PD. However little is known about the causes of this alteration. Most of the cytopathological findings of this disease have been obtained from cellular and animal experimental models but studies in human tissue are scarce. Our previous studies, using cellular models of Parkinson ́s disease, demonstrate that fragmentation is an early event, previous to a-synuclein aggregation and cytoskeletal alterations. The purpose of this study was to analyze the Golgi complex of dopaminergic neurons in the substantia nigra of PD necropsies using morphological and biochemical techniques. At light microscopy, the Golgi apparatus appeared fragmented and distributed throughout the cytoplasm. Electron microscopy demonstrated that the Golgi ribbon is altered but the typical stacked appearance of this organelle is not lost. The biochemical analysis showed altered levels of GTPases and Golgi structural proteins. We also observed main alterations in the distribution of Rab1 and the SNARE protein syntaxin 5, which is accumulated mainly out of the cell in extracellular inclusions. We demonstrate for the first time that the expression of Golgi structural and transport regulatory proteins is altered in human samples of PD which may explain the fragmentation of this organelle. These alterations may disturb the trafficking of many proteins that are essential for neuronal function.