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Published on: January 7, 2014
Chronic MPTP in Mice Damage-specific Neuronal Phenotypes within Dorsal Laminae of the Spinal Cord
Francesca Biagioni1, Giorgio Vivacqua2,3, Gloria Lazzeri4
1I.R.C.C.S. Neuromed, via dell'Elettronica, Pozzilli, Italy.
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.
Insights
The neurotoxin MPTP causes parkinsonism and damages spinal cord sensory neurons. This study shows MPTP exposure alters specific dorsal horn neurons and increases alpha-synuclein, mirroring Parkinson's disease pathology.
Area of Science:
- Neuroscience
- Neurotoxicology
- Spinal Cord Research
Background:
- Parkinson's disease (PD) involves neuronal damage beyond the brain, affecting the spinal cord.
- Alpha-synuclein aggregates are found in the spinal cord dorsal horn in PD patients.
- The impact of MPTP (1-methyl, 4-phenyl, 1, 2, 3, 6-tetrahydropiridine) on the sensory spinal cord is not well understood.
Purpose of the Study:
- To investigate the pathological effects of chronic MPTP exposure on the dorsal spinal cord.
- To determine if MPTP induces changes in specific neuronal populations and alpha-synuclein expression in the sensory compartment of the spinal cord.
Main Methods:
- Mice were chronically exposed to low doses of MPTP (5 mg/kg twice daily for 21 days).
- Quantitative stereology was used to assess dopamine neuron survival.
- Immunohistochemistry was employed to evaluate neuronal markers (enkephalin, calretinin, calbindin D28K, parvalbumin) and alpha-synuclein expression in the dorsal spinal cord.
Main Results:
- MPTP treatment selectively damaged nigrostriatal dopamine axon terminals without reducing nigral neuron numbers.
- A significant decrease in enkephalin-, calretinin-, calbindin D28K-, and parvalbumin-positive neurons was observed in dorsal spinal cord laminae I-III.
- Met-enkephalin and substance P fibers were reduced, while alpha-synuclein immunoreactivity markedly increased in laminae I and II.
Conclusions:
- Chronic MPTP exposure causes loss of specific dorsal spinal cord neurons involved in sensory transmission and pain modulation.
- This study provides the first experimental evidence linking MPTP-induced parkinsonism to sensory pathway alterations in the spinal cord.
- The findings offer an experimental correlate for sensory and pain disturbances observed in Parkinson's disease patients.
