Brain aging, memory impairment and oxidative stress: a study in Drosophila melanogaster

Behav Brain Res. 2014 Feb 1;259:60-9. doi: 10.1016/j.bbr.2013.10.036. Epub 2013 Oct 30.

Abstract

Memory impairment during aging is believed to be a consequence of decline in neuronal function and increase in neurodegeneration. Accumulation of oxidative damage and reduction of antioxidant defense system play a key role in organismal aging and functional senescence. In our study, we examined the age-related memory impairment (AMI) in relation to oxidative stress using Drosophila model. We observed a decline in cognitive function in old flies with respect to both short-lived and consolidated forms of olfactory memory. Light and electron microscopy of mushroom bodies revealed a reduction in the number of synapses and discernible architectural defects in mitochondria. An increase in neuronal apoptosis in Kenyon cells was also evident in aged flies. Biochemical investigations revealed a comparable age-associated decrease in the activity of antioxidant enzymes such as catalase and superoxide dismutase as well as the GSH level, accompanied by an increase in the level of lipid peroxidation and generation of reactive oxygen species in the brain. There was no significant difference in the activity level of AChE and BChE enzymes between different age groups while immunohistochemical studies showed a significant decrease in the level of ChAT in 50-day-old flies. RNAi-mediated silencing of cat and sod1 genes caused severe memory impairment in 15-day-old flies, whereas, over-expression of cat gene could partially rescue the memory loss in the old flies. We demonstrated that a Drosophila long-lived strain, possessing enhanced activity of antioxidant enzymes and higher rate of resistance to oxidative stress, shows lower extent of AMI compared to normal lifespan strain. Present study provides evidence for involvement of oxidative stress in AMI in Drosophila.

Keywords: Age-related memory impairment; Aging; Classical olfactory conditioning; Oxidative stress.

MeSH terms

  • Acetylcholine / metabolism
  • Aging* / genetics
  • Animals
  • Animals, Genetically Modified
  • Brain / metabolism
  • Brain / pathology*
  • Brain / ultrastructure
  • Catalase / genetics
  • Catalase / metabolism
  • Choline / analogs & derivatives
  • Choline / metabolism
  • Choline O-Acetyltransferase / metabolism
  • Conditioning, Classical / physiology
  • Drosophila Proteins / genetics
  • Drosophila melanogaster / physiology*
  • Gene Expression Regulation / genetics
  • Glutathione / metabolism
  • Lipid Peroxidation / genetics
  • Memory Disorders / genetics
  • Memory Disorders / pathology*
  • Mushroom Bodies / metabolism
  • Oxidative Stress / physiology*
  • Reactive Oxygen Species / metabolism
  • Smell / physiology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Time Factors

Substances

  • Drosophila Proteins
  • Reactive Oxygen Species
  • butyrylcholine
  • Catalase
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Choline O-Acetyltransferase
  • Glutathione
  • Choline
  • Acetylcholine