MPTP-treated mice: long-lasting loss of nigral TH-ir neurons but not paradoxical sleep alterations

Abstract

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse model is widely used for studying Parkinson's disease. A previous study in our laboratory showed that MPTP-treated mice presented an increase in paradoxical sleep (PS) throughout the sleep/wakefulness cycle. However, many researchers have reported a behavioural and dopaminergic neuron recovery process which appears some time after MPTP treatment. Hence, in a first step, we decided to study tyrosine hydroxylase-immunoreactive (TH-ir) neuron loss in the nigrostriatal pathway 7, 15, 40 and 60 days after MPTP injection. We then studied S/W in MPTP-treated mice 20 days and 40 days after MPTP injection. Our results showed that MPTP-treated mice presented a 30% reduction in the number of TH-ir neurons in the substantia nigra and a 50% decrease in striatal TH staining, compared with saline-treated mice. These nigrostriatal pathway alterations are stable until 60 days post-MPTP treatment. The PS increase observed in our previous study was also observed in the present work 20 days after MPTP treatment but not after 40 days. The present results demonstrated that TH-ir neuronal loss in MPTP mice is quite stable until 60 days, whereas PS alterations are not. This finding suggests that there is no correlation between the dopaminergic neuronal loss and PS alteration in MPTP-treated mice. Hence, other neurotransmission systems may be involved in PS amount variations in MPTP mice and it is possible that the PS increase is accounted for by a homeostatic process, following a hypothetical reduction in this sleep state.