The involvement of spinal cord in MPTP-induced neurotoxicity: morphological evidence

Parkinson Disease (PD) is the prototype of synucleinopathies, a group of neurodegenerative disorders characterized by the accumulation of alpha-synuclein (α-syn). The involvement of spinal cord (SC) in PD is described in human autopsies, clinical reports and experimental studies [1]. The neurotoxin MPTP reproduces to a remarkable extent neuropathology of PD [2]. Furthermore, recent studies have shown that MPTP, besides dopaminergic neurons, affects also spinal Motor Neurons (MNs) [3]. To detect the effects of different MPTP treatments on the neuropathology in the SC at different ages and in different animal species. Following MPTP, neurotoxicity involves the whole thoraco-lumbar spinal cord. A model-dependent variation in the pattern of α-syn immunostaining has been detected. MNs, sympathetic pre-ganglionic neurons and calbindin immunoreactive (IR) cells of lamina VII are mostly affected, whereas TH positive fibers are spared. Alterations in α-syn positive fibers occur in the posterior laminae (I, II and III) and correlate with a significant loss of Met-Enk, SP and calbindin 28 kDa. A-syn accumulates in the affected neurons and in glial cells. Our results indicate that the SC represents a target of the parkinsonism-inducing neurotoxin MPTP. These data suggest that altered α-syn distribution associates with MPTP-induced neurotoxicity.