Mortality, oxidative stress and tau accumulation during ageing in parkin null mice

J Neurochem. 2007 Oct;103(1):98-114. doi: 10.1111/j.1471-4159.2007.04762.x. Epub 2007 Jul 10.

Abstract

Young parkin null (pk-/-) mice have subtle abnormalities of behaviour, dopamine (DA) neurotransmission and free radical production, but no massive loss of DA neurons. We investigated whether these findings are maintained while ageing. Pk-/- mice have reduced life span and age-related reduced exploratory behaviour, abnormal walking and posture, and behaviours similar to those of early Parkinson's disease (PD), reduced number of nigrostriatal DA neurons and proapoptotic shifts in the survival/death proteins in midbrain and striatum. Contrary to young pk-/- animals 24-month-old pk-/- mice do not have compensatory elevation of GSH in striatum, glutathione reductase (GR) and glutathione peroxidase (GPx) activities are increased and catalase unchanged. Aged pk-/- mice accumulate high levels of tau and fail to up-regulate CHIP and HSP70. Our results suggest that aged pk-/- mice lack of the compensatory mechanisms that maintain a relatively normal DA function in early adulthood. This study could help to explain the effects of ageing in patients with genetic risks for Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Cell Count
  • Disease Models, Animal
  • Disease Progression
  • Dopamine / metabolism
  • Exploratory Behavior
  • Male
  • Mesencephalon / pathology
  • Mice
  • Mice, Knockout
  • Mice, Neurologic Mutants
  • Motor Activity / genetics
  • Oxidative Stress / genetics
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / pathology
  • Parkinsonian Disorders / physiopathology*
  • Posture
  • Substantia Nigra / pathology
  • Survival Rate
  • Ubiquitin-Protein Ligases / deficiency*
  • Ubiquitin-Protein Ligases / genetics
  • tau Proteins / metabolism*

Substances

  • tau Proteins
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Dopamine