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

Abstract

The model of accelerated senescence with the prolonged administration of d-galactose is used in anti-aging studies because it mimics several aging-associated alterations such as increase of oxidative stress and decline of cognition. However, there is no standardized protocol for this aging model, and recently some reports have questioned its effectiveness. To clarify this issue, we used a model of high-dose d-galactose on 1-month-old male Wistar rats and studied the hippocampus, one of the most affected brain regions. In one group (n = 10), d-galactose was daily administered intraperitoneally (300 mg/kg) during 8 weeks whereas age-matched controls (n = 10) were injected intraperitoneally with saline. A third group (n = 10) was treated with the same dose of d-galactose and with oral epigallocatechin-3-gallate (EGCG) (2 grams/L), a green tea catechin with anti-oxidant and neuroprotective properties. After treatments, animals were submitted to open-field, elevated plus-maze and Morris water maze tests, and neurogenesis in the dentate gyrus subgranular layer was quantified. There were no significant alterations when the three groups were compared in the number of doublecortin-and Ki-67-immunoreactive cells, and also on anxiety levels, spatial learning, and memory. Therefore, d-galactose was not effective in the induction of accelerated aging, and EGCG administered to d-galactose-treated animals did not improve behavior and had no effects on neurogenesis. We conclude that daily 300 mg/kg of d-galactose administered intraperitoneally may not be a suitable model for inducing age-related neurobehavioral alterations in young male Wistar rats. More studies are necessary to obtain a reliable and reproducible model of accelerated senescence in rodents using d-galactose.

Antioxidative, anti-inflammatory and anti-apoptotic effects of ellagic acid in liver and brain of rats treated by D-galactose

“…Accumulated evidence shows that ROS-induced oxidative stress is the key factor in inducing natural age-related changes 33 . D-gal induces ageing alterations that are similar to the normal ageing processes 34 , 35 . It has been confirmed in previous studies that oxidative stress could result in apoptosis, which is the main cause of many types of organ damage.…”

Sexual Dimorphism in the Behavioral Responses and the Immunoendocrine Status in d-Galactose-Induced Aging

“…In males, the main effect was the dose-dependent increase in horizontal and vertical exploratory activity in the open field, which is opposed to what should be expected in an induced aging ( 2 ). A trend of increased total locomotor activity and thigmotaxis (inner zone) of the open field has been recently reported in young male Wistar rats treated with 300 mg/kg d -gal ( 24 ). As before, the results obtained with d -gal in the open field may vary depending on the strain used ( 23 ) because anxiety levels exhibited in this test are strongly determined by this factor ( 44 ).…”

“…Discrepancies are also found when studied in rats ( 21–23 ). Thus, the most recent scientific literature complains about the lack of consistency of chronic d -gal inducing accelerated-aging changes in behavioral outcomes ( 24 ).…”

Evaluation of Acute and Chronic Effects of D-Galactose on Memory and Learning in Wistar Rats

“…A few studies have shown that this is not a standard model, as these changes produced are not consistent across all species and ages. 6) …”