Behavioral deficit, oxidative stress, and mitochondrial dysfunction precede tau pathology in P301S transgenic mice. Academic Article uri icon

Overview

MeSH

  • Aging
  • Animals
  • Citric Acid Cycle
  • Electron Transport
  • Exploratory Behavior
  • Female
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinase 3 beta
  • Locomotion
  • Male
  • Mice
  • Mice, Transgenic
  • Reactive Oxygen Species
  • Spatial Behavior

MeSH Major

  • Behavior, Animal
  • Mitochondria
  • Oxidative Stress
  • Tauopathies

abstract

  • Abnormal tau accumulation can lead to the development of neurodegenerative diseases. P301S mice overexpress the human tau mutated gene, resulting in tau hyperphosphorylation and tangle formation. Mice also develop synaptic deficits and microglial activation prior to any neurodegeneration and tangles. Oxidative stress can also affect tauopathy. We studied the role of oxidative stress in relationship to behavioral abnormalities and disease progression in P301S mice at 2, 7, and 10 mo of age. At 7 mo of age, P301S mice had behavioral abnormalities, such as hyperactivity and disinhibition. At the same age, we observed increased carbonyls in P301S mitochondria (∼215 and 55% increase, males/females), and deregulation in the activity and content of mitochondrial enzymes involved in reactive oxygen species formation and energy metabolism, such as citrate synthase (∼19 and ∼5% decrease, males/females), MnSOD (∼16% decrease, males only), cytochrome C (∼19% decrease, females only), and cytochrome C oxidase (∼20% increase, females only). These changes in mitochondria proteome appeared before tau hyperphosphorylation and tangle formation, which were observed at 10 mo and were associated with GSK3β activation. At that age, mitochondria proteome deregulation became more apparent in male P301S mitochondria. The data strongly suggest that oxidative stress and mitochondrial abnormalities appear prior to tau pathology.

publication date

  • November 2011

has subject area

  • Aging
  • Animals
  • Behavior, Animal
  • Citric Acid Cycle
  • Electron Transport
  • Exploratory Behavior
  • Female
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinase 3 beta
  • Locomotion
  • Male
  • Mice
  • Mice, Transgenic
  • Mitochondria
  • Oxidative Stress
  • Reactive Oxygen Species
  • Spatial Behavior
  • Tauopathies

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3205832

Digital Object Identifier (DOI)

  • 10.1096/fj.11-186650

PubMed ID

  • 21825035

Additional Document Info

start page

  • 4063

end page

  • 4072

volume

  • 25

number

  • 11