The toxin MPTP generates similar cognitive and locomotor deficits in hTau and tau knock-out mice

Brain Res. 2019 May 15;1711:106-114. doi: 10.1016/j.brainres.2019.01.016. Epub 2019 Jan 11.

Abstract

Parkinson's disease (PD) is characterized by motor deficits, although cognitive disturbances are frequent and have been noted early in the disease. The main pathological characteristics of PD are the loss of dopaminergic neurons and the presence of aggregated α-synuclein in Lewy bodies of surviving cells. Studies have also documented the presence of other proteins within Lewy bodies, particularly tau, a microtubule-associated protein implicated in a wide range of neurodegenerative diseases, including Alzheimer's disease (AD). In AD, tau pathology correlates with cognitive dysfunction, and tau mutations have been reported to lead to dementia associated with parkinsonism. However, the role of tau in PD pathogenesis remains unclear. To address this question, we induced parkinsonism by injecting the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in hTau mice, a mouse model of tauopathy expressing human tau, and a mouse model knock-out for tau (TKO). We found that although MPTP impaired locomotion (gait analysis) and cognition (Barnes maze), there were no discernable differences between hTau and TKO mice. MPTP also induced a slight but significant increase in tau phosphorylation (Thr205) in the hippocampus of hTau mice, as well as a significant decrease in the soluble and insoluble tau fractions that correlated with the loss of dopaminergic neurons in the brainstem. Overall, our findings suggest that, although MPTP can induce an increase in tau phosphorylation at specific epitopes, tau does not seem to causally contribute to cognitive and locomotor deficits induced by this toxin.

Keywords: Cognition; Locomotion; MPTP; Parkinson’s disease; Tau; Tauopathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / metabolism*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Animals
  • Brain / metabolism
  • Cognition / physiology
  • Disease Models, Animal
  • Dopaminergic Neurons / metabolism
  • Female
  • Hippocampus / metabolism
  • Humans
  • Locomotion / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Phosphorylation
  • Tauopathies / metabolism*
  • Tauopathies / physiopathology
  • alpha-Synuclein / metabolism
  • tau Proteins / metabolism*

Substances

  • alpha-Synuclein
  • tau Proteins
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine