MPTP toxicity causes vocal, auditory, orientation and movement defects in the echolocation bat.

Abstract

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can damage dopaminergic neurons in the substantia nigra in many mammals with biochemical and cellular changes that are relatively similar to those observed in Parkinson's disease. Our study examined whether MPTP-treated echolocation bats can cause changes in bat echolocation system. By considering ultrasound spectrums, auditory brainstem-evoked potentials and flight trajectories of normal bats, we observed that the vocal, auditory, orientation and movement functions of MPTP-treated bats were significantly impaired, and they exhibited various symptoms resembling those in patients with Parkinson's disease. Our immunohistochemistry and western blot analyses further indicated that expression of vocal-related FOXP2 in the superior colliculus, auditory-related otoferlin in the inferior colliculus, dopamine synthesis-related aromatic l-amino acid decarboxylase in the substantia nigra and dopamine receptor in the striatum was significantly decreased. Furthermore, protein expression related to inflammation, oxidative stress and apoptosis in the substantia nigra was significantly increased in MPTP-treated bats. These results indicate that inflammation, oxidative stress and apoptosis may be instrumental in dopaminergic neurodegeneration in the substantia nigra. The vocal, auditory and orientation and movement dysfunctions of MPTP-treated bats are relatively consistent with symptoms of Parkinson's disease.