Profiles of brain oxidative damage, ventricular alterations, and neurochemical metabolites in the striatum of PINK1 knockout rats as functions of age and gender: Relevance to Parkinson disease

Free Radic Biol Med. 2019 Nov 1:143:146-152. doi: 10.1016/j.freeradbiomed.2019.08.008. Epub 2019 Aug 8.

Abstract

Parkinson disease (PD) is the second most common neurodegenerative disease associated with aging. Dopaminergic neuronal degeneration and α-synuclein aggregation are commonly found in PD brain. Oxidative damage and inflammation often are considered as etiological factors of PD, although the detailed mechanisms still remain unknown. Gender and aging are two important risk factors to PD, and gene mutations and certain environmental factors have been implicated in this disease. The current study employed PTEN-induced putative kinase -1 (PINK1) knockout (KO) rats, since mutations in PINK-1 lead to familial PD. We evaluated the oxidative damage in the brain of PINK1 KO rats, and we used MRI and MRS to measure the ventricle sizes and neurochemical metabolite profiles in these rats as a function of age and gender. Distinct gender- and age-related alterations were found. The results are discussed with respect to the suitabililty of this unique rat as a faithful model of known characteristics of PD.

Keywords: Edema; Gender differences; MRS; Oxidative damage; Parkinson disease; Pink1 KO rats; Striatum; Ventricular system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Biomarkers / metabolism
  • Brain / metabolism*
  • Brain / pathology*
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Female
  • Gene Knockout Techniques
  • Glutamine / metabolism
  • Glutathione / metabolism
  • Inositol / metabolism
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Neurodegenerative Diseases / metabolism
  • Oxidative Stress*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Protein Kinases / genetics*
  • Rats
  • Taurine / metabolism
  • Taurine / pharmacology

Substances

  • Biomarkers
  • Glutamine
  • Taurine
  • Aspartic Acid
  • Inositol
  • N-acetylaspartate
  • Protein Kinases
  • PTEN-induced putative kinase
  • Glutathione