Evaluation of Nigrostriatal Neurodegeneration and Neuroinflammation Following Repeated Intranasal 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Administration in Mice, an Experimental Model of Parkinson’s Disease

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population older than 60 years. The administration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice is the most widely used approach to elucidate the mechanisms of cell death involved in PD. However, the magnitude of the PD-like neurodegeneration induced by MPTP depends on many variables, including the regimen of its administration. It has been demonstrated that intranasal (i.n.) administration of MPTP constitutes a new route of toxin delivery to the brain that mimics environmental exposure to neurotoxins. Previous data showed that mice submitted to chronic and acute i.n. MPTP treatment displayed a robust (~80%) and moderate (~55%) loss of striatal dopamine, respectively. However, little is known about the neurodegenerative and neuroinflammatory processes following a subacute i.n. MPTP administration in mice. Here, the C57BL/6 mice were infused intranasally with MPTP (1 mg/nostril/day) during 4 consecutive days. At 7 and 28 days after the last administration, the subacute i.n. MPTP regime decreased the tyrosine hydroxylase (TH)-labeling in the striatum (40-50%) and substantia nigra (25-30%) and increased the astrogliosis in such brain areas at both time points. Taken together, our data showed that the subacute administration of MPTP into the nasal cavity of C57BL/6 mice induces long-lasting neurodegeneration and neuroinflammation in the nigrostriatal pathway, thus representing a valuable animal model for the investigation of neuroprotective strategies in PD.

A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson’s disease

“…Indeed, the intranasal route is known to bypass the blood-brain barrier through olfactory-and trigeminal-associated extracellular pathways, allowing entry of agents to the CNS, as shown for insulin-like growth factor-1 (ref. toxin delivery in the brain that mimics environmental exposure to neurotoxins 33 , further demonstrating the ability of chemicals to get from the olfactory bulb to the nigrostriatal pathway, as shown recently using Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging 34 . To determine whether delivery of PX3 peptide into the brain could also be achieved by intranasal administration, we performed experiments using radiolabelled PX3, and analysed its distribution in several peripheral organs and in the CNS (Table 1).…”

In vivo NMR studies of regional cerebral energetics in MPTP model of Parkinson's disease: recovery of cerebral metabolism with acute levodopa treatment

“…) and MPTP induced SNc dopaminergic lesion (Tristao et al . ). Microglial activation was seen from 1st to 14th day in the SNc and in the striatum following MPTP insult in mice (Czlonkowska et al .…”

Environmental Toxicants-Induced Immune Responses in the Olfactory Mucosa

“…Of interest, it was shown that either intranasally administered influenza virus, LPS, or MPTP (a synthetic neurotoxicant) caused selective decreases of dopamine neurons in the substantia nigra of mice (21, 27, 77–79). The route from the OM to the substantia nigra, however, remains to be elucidated.…”