A high dose of short term exogenous D-galactose administration in young male rats produces symptoms simulating the natural aging process

Aims: D-Galactose (D-gal) induced accelerated senescence has been used to develop an aging model for brain. Previously, long term administration of a wide range of doses has been used for this purpose. In the present study we investigate whether short term administration of a high dose of D-gal in rats induces significant signs and symptoms similar to natural aging.

Main methods: Young rats were injected intraperitoneally with D-gal at a dose of 300 mg/ml/kg for one week. Behavioral analysis for depression and anxiety like symptoms were monitored by forced swim test (FST) and LIGHT/dark transition (LDT) test. Assessment of memory was done using the Morris water maze (MWM), passive avoidance test (PAT) and elevated plus maze (EPM) test. Biochemical analysis was done for estimation of antioxidant Enzymes and acetylcholinesterase. Determination of brain biogenic amines was performed by HPLC-EC.

Key findings: Short term administration of D-gal significantly altered behavioral, biochemical and neurochemical responses in rats. D-Gal injected rats exhibited depressogenic and anxiogenic behaviors while memory was also significantly impaired in these rats. Brain lipid peroxidation and superoxide dismutase activity were significantly increased while catalase and Glutathione Peroxidase decreased. Increased activity of acetylcholinesterase was also exhibited by D-gal injected rats while brain biogenic amines were significantly decreased. Food intake and growth rate were however comparable in both groups.

Significance: Together the behavioral, biochemical and neurochemical impairments following the high dose of D-gal suggest that symptoms similar to natural aging may be developed in rats in as early as one week.

Behaviors; Neurotransmitters; Oxidative stress; d-Galactose.