1-Methyl, 4-phenyl, 1,2,3,6-tetrahydropiridine (
MPTP) is a
neurotoxin, widely used to produce experimental models of
Parkinson Disease in rodents and primates. Although dopaminergic neurons are the most sensitive to
MPTP neurotoxicity, different neuronal subtypes are affected. Among these, recent studies indicate that
MPTP may produce pathological effects on spinal neurons. In fact,
MPTP activates apoptotic
proteins within the spinal cord and in particular within the motor neurons, suggesting commonalities between
Parkinson Disease and
Amyotrophic Lateral Sclerosis. In order to assess this point, in the present study we measured whether
MPTP produces motor neurons loss. We chose a dose of
MPTP (20 mg/kg × 3, 2 h apart), which in C57BL/6N mice was able to induce a massive nigrostriatal damage. Since both
Parkinson Disease and
Amyotrophic Lateral Sclerosis are characterized by altered
alpha-synuclein immunostaining, this
protein was also evaluated within spinal motor neurons, following
MPTP administration. Three different
monoclonal antibodies, recognizing distinct
epitopes in the sequence of
alpha-synuclein were used. Severe dopaminergic cell loss was quantified by stereology within the substantia nigra pars compacta, along with marked decrease of striatal
tyrosine hydroxylase densitometry. The same doses of
MPTP also caused a significant motor neuron loss in the spinal cord (roughly 30%). Spared motor neurons appeared often dysmorphic and vacuolated and possessed altered
alpha-synuclein immunostaining. This latter finding extended to other cell types of the spinal cord. These data indicate that
MPTP, apart from being a dopaminergic
neurotoxin, produces also motor neuron death, thus bridging
experimental Parkinsonism and
motor neuron disease.