Risk is in the air: an intranasal MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) rat model of Parkinson's disease

Abstract

The presence of smell loss and the early pathological involvement of the olfactory pathways in the early stages of some neurodegenerative disorders are in accord with the tenants of the olfactory vector hypothesis. This hypothesis postulates that some such diseases may be caused or catalyzed by agents that enter the brain via the olfactory mucosa. In this study, rats infused intranasally (i.n.) with a low concentration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) subsequently suffered olfactory, cognitive, and motor function impairments conceivably analogous to those observed during different stages of the development of Parkinson's disease (PD). Such infusion decreased the expression of the enzyme tyrosine hydroxylase in the olfactory bulb and substantia nigra by means of apoptotic mechanisms, reducing dopamine levels in different brain structures, such as the olfactory bulb, striatum, and prefrontal cortex. These findings reinforce the suggestion that the olfactory system may be a particularly sensitive route for the penetration of xenobiotic agents into the central nervous system and that the i.n. MPTP rat model may provide insight into the underlying mechanisms of PD pathogenesis, potentially leading to the development of new therapeutic strategies for this devastating disease.