Abstract
The neurotoxin 1-methyl, 4-phenyl, 1, 2, 3, 6-tetrahydropiridine (MPTP) is widely used to produce experimental parkinsonism. Such a disease is characterized by neuronal damage in multiple regions beyond the nigrostriatal pathway including the spinal cord. The neurotoxin MPTP damages spinal motor neurons. So far, in Parkinson’s disease (PD) patients alpha-synuclein aggregates are described in the dorsal horn of the spinal cord. Nonetheless, no experimental investigation was carried out to document whether MPTP affects the sensory compartment of the spinal cord. Thus, in the present study, we investigated whether chronic exposure to small doses of MPTP (5 mg/kg/X2, daily, for 21 days) produces any pathological effect within dorsal spinal cord. This mild neurotoxic protocol produces a damage only to nigrostriatal dopamine (DA) axon terminals with no decrease in DA nigral neurons assessed by quantitative stereology. In these experimental conditions we documented a decrease in enkephalin-, calretinin-, calbindin D28K-, and parvalbumin-positive neurons within lamina I and II and the outer lamina III. Met-Enkephalin and substance P positive fibers are reduced in laminae I and II of chronically MPTP-treated mice. In contrast, as reported in PD patients, alpha-synuclein is markedly increased within spared neurons and fibers of lamina I and II after MPTP exposure. This is the first evidence that experimental parkinsonism produces the loss of specific neurons of the dorsal spinal cord, which are likely to be involved in sensory transmission and in pain modulation providing an experimental correlate for sensory and pain alterations in PD.
Highlights
Francesca Biagioni and Giorgio Vivacqua contributed to this work.Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disease (Ascherio et al 2016)
Densitometric analysis of TH+ terminals confirms the occurrence of a slight decrease of TH immunostaining within the dorsal striatum of MPTP-treated mice, compared with scale bar 200 μm) as reported in the graph measuring optical density. b Representative pictures from TH immune-stained substantia nigra where no neuronal loss is present as measured in the graph reporting stereological counts
The count of T H+ cell bodies within the substantia nigra pars compacta (SNpc) provided by stereology count demonstrates that the number of nigral T H+ neurons is not affected by this protocol of chronic MPTP exposure (Fig. 1b)
Summary
Francesca Biagioni and Giorgio Vivacqua contributed to this work.Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disease (Ascherio et al 2016). Neurodegeneration may involve other areas of the CNS, including spinal cord (Vivacqua et al 2011a; Del Tredici and Braak 2012; Ferrucci et al 2013; Yeh et al 2016). The involvement of the spinal cord was suggested to underlay specific non-motor symptoms of PD, such as pain, orthostatic hypotension, or urinary dysfunctions (Natale et al 2013; Schapira et al 2017; Poewe et al 2017). Neuropathological studies detected degeneration of both autonomic regions and dorsal laminae in the spinal cord of PD patients (Braak et al 2007; Del Tredici and Braak 2012). Alterations of specific dorsal intra-spinal circuits and/or degeneration of descending pathways from the brainstem (Del Tredici and Braak 2012; Surmeier et al 2017) to the dorsal laminae could contribute to the development of non-motor symptoms of PD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
