D-Galactose Effectiveness in Modeling Aging and Therapeutic Antioxidant Treatment in Mice

Abstract

Accumulating evidence suggests that mitochondrial dysfunction and oxidative stress play major roles in aging. Chronic administration of D-galactose has been reported to cause deterioration of cognitive and motor skills that are similar to symptoms of aging and, therefore, is regarded as a model of accelerated aging. Because enhancing endogenous antioxidants is now widely regarded as an attractive therapy for conditions associated with mitochondrial oxidative stress, in the present study the effects of a-lipoic acid, L-carnitine, and PMX-500F on D-galactose treated mice were tested. Female mice were injected with (100 mg/kg) D-(þ)-galactose for 6 weeks and some groups were treated with a daily dose of a-lipoic acid (5 mg/kg), L-carnitine (3.9 mg/kg), PMX-500F (11.9 mg/kg), or the vehicle (0.1 M Tris, pH 7.4). Control mice were treated with physiological saline. An accelerating Rota-Rod, open field test, and Y-maze test were performed, and serum lactate concentrations were analyzed. These analyses did not identify impairment in motor coordination, open-field activity, or spatial memory ( p > 0.05). Similarly, serum lactate concentrations in D-galactose-treated mice were not elevated when compared to controls ( p > 0.05). Treatment with the antioxidant compounds at the given concentrations did not result in any changes in the behavioral parameters tested. In conclusion, results of this study illustrate that chronic, short-term D-galactose treatment may not represent a suitable model for inducing readily detectable age-related neurobehavioral symptoms in mice.

The Effect of Green Tea Leaf Extract on Spatial Memory Function and Superoxyde Dismutase Enzyme Activity in Mice with D-galactose Induced Dimentia

“…Mice in the control group also had difficulty in remembering the location of the platform, shown by the low percentage of time needed in the target quadrant in the retention phase of morris water maze (MWM) assay. This is consistent with the finding of the previous studies showing that subcutaneous injection of D galactose at a 150 mg/kg daily for 6 weeks can cause memory and behavioral impairment in mice (Parameshwaran et al, 2010;Miao et al, 2009). D-galactose is also known to cause spatial memory and neurocell damage due to cellular metabolic damage by lowering the activity of Na + , K + -ATPase enzymes and increasing oxidative stress through increased lipid peroxidation and decreased antioxidant enzyme activity (Miao et al, 2009).…”

D-Galactose Induces a Mitochondrial Complex I Deficiency in Mouse Skeletal Muscle: Potential Benefits of Nutrient Combination in Ameliorating Muscle Impairment

“…In our study, 8-week-old mice demonstrated no memory loss, which is consistent with a recent study. 2 This suggests that the age of the mice may also be a key factor in learning and memory, especially in the premature aging model.…”

d-Galactose High-Dose Administration Failed to Induce Accelerated Aging Changes in Neurogenesis, Anxiety, and Spatial Memory on Young Male Wistar Rats

“…16,17 It is important to note that, more recently, some dissonant reports concerning the effectiveness of this accelerated aging paradigm have been published. [18][19][20] Indeed, Parameshwaran and collaborators have concluded that the d-galactose treatment (intraperitoneal [i.p] injection of 100 mg/kg per day) in female C57BL/61 mice was not suitable for testing antioxidant compounds in mice. 18 Moreover, Tikhonova and collaborators found that d-galactose treatment (i.p.…”