The neurobiology of the spinal cord in experimental parkinsonism and Parkinson's disease

The neurobiology of non-motor symptoms in Parkinson's disease (PD) reveals a number of unexpected areas which once were not recognized a priori as part of the neuropathology underlying PD. These areas may belong either to central nervous system or periphery. Among central areas major efforts in the last decade led to recognize a number of brain nuclei as part of the disease spreading or disease onset in PD patients. Unexpectedly recent evidence deriving from pathological studies in PD patients and corroborated by experimental models of PD provided clear evidence that the spinal cord is often recruited in PD pathology. Such an involvement is intriguing since the major degenerative disease of the spinal cord (amyotrophic lateral sclerosis) features the involvement of dopaminergic neurons of the substantia nigra pars compacta, while some environmental (parkinsonism, ALS, and dementia of Guam) and genetic (Kufor-Rakeb syndrome) diseases are known to be characterized by mixed degeneration o

The neurobiology of non-motor symptoms in Parkinson's disease (PD) reveals a number of unexpected areas which once were not recognized a priori as part of the neuropathology underlying PD. These areas may belong either to central nervous system or periphery. Among central areas major efforts in the last decade led to recognize a number of brain nuclei as part of the disease spreading or disease onset in PD patients. Unexpectedly recent evidence deriving from pathological studies in PD patients and corroborated by experimental models of PD provided clear evidence that the spinal cord is often recruited in PD pathology. Such an involvement is intriguing since the major degenerative disease of the spinal cord (amyotrophic lateral sclerosis) features the involvement of dopaminergic neurons of the substantia nigra pars compacta, while some environmental (parkinsonism, ALS, and dementia of Guam) and genetic (Kufor-Rakeb syndrome) diseases are known to be characterized by mixed degeneration of pyramidal and extrapyramidal regions. Thus, the clear-cut between degeneration of dopaminergic neurons in the substantia nigra and the loss of pyramidal motor system appears now more as a continuum of degeneration which converge in abnormal activity and cell pathology of motor neurons as a final common pathway. Among motor neurons, visceral efferent cells of the spinal cord are involved and provide a robust neurobiological findings which may justify a variety of non-motor autonomic symptoms which characterize PD. Neurodegeneration in the spinal cord extends to the dorsal horn of the grey matter posing an intriguing link between PD and sensory alterations. The present manuscript reviews the involvement of multiple regions of the spinal cord in PD and experimental parkinsonism in the attempt to provide both a neurobiological background to understand non motor symptoms and to provide the anatomical basis for disease spreading.