Adenosine protects D-galactose induced alterations in rat model of aging via attenuating neurochemical profile and redox status

Metab Brain Dis. 2022 Oct;37(7):2483-2496. doi: 10.1007/s11011-022-01049-7. Epub 2022 Jul 23.

Abstract

Aging is the process that every organism faces. The aging model of brain has been developed by the use of d-galactose (d-Gal). Adenosine (Ad) being a neuroprotective agent that has been utilized in treatment of various neurological disorders. The aim of current study is to evaluate the outcome of Ad on d-Gal induced neurotoxicity which caused behavioral deficits, memory impairment and oxidative stress. Rats were treated with d-Gal at a dose of 300 mg/ml/kg and Ad 1 mg/ml/kg; intraperitoneally for 28 days. Behavioral assessment was performed after the treatment period. Animals were sacrificed after behavioral tests and their brains were collected, hippocampus were removed for biochemical and neurochemical analysis. The results showed that administration of Ad ameliorates the negative effects of d-Gal induced aging in various behavioral tests and increased the time spent in the open arm and light box in elevated plus maze (EPM) and light dark activity (LDA) tests respectively indicate anxiolytic effect; increased the mobility time in tail suspension test (TST) shows antidepressant effect; decreased escape latencies in Morris water maze (MWM) acquisition trials, increase entries and time spent in the target quadrant suggests improvement in learning ability of animals. Administration of Ad also decreased malondialdehyde (MDA) levels, increased antioxidant enzymes activity; decreased acetylcholinesterase (AChE) activity, increased 5-hydroxytryptamine (5-HT, serotonin) metabolism and normalized histopathological alteration in the hippocampus. It is concluded that anxiety, depression and memory impairment induced by d-Gal were protected by Ad through its antioxidant and neuro-modulatory effects.

Keywords: Adenosine; Aging; Anti-oxidant enzyme; Anxiety; D-galactose; Depression; Memory; Oxidative stress; Serotonin metabolism.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Adenosine / pharmacology
  • Aging / metabolism
  • Animals
  • Anti-Anxiety Agents* / pharmacology
  • Antioxidants / therapeutic use
  • Galactose / toxicity
  • Malondialdehyde / metabolism
  • Maze Learning
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Oxidation-Reduction
  • Oxidative Stress
  • Rats
  • Serotonin / metabolism

Substances

  • Galactose
  • Serotonin
  • Acetylcholinesterase
  • Neuroprotective Agents
  • Antioxidants
  • Adenosine
  • Anti-Anxiety Agents
  • Malondialdehyde