D-Galactose High-Dose Administration Failed to Induce Accelerated Aging Changes in Neurogenesis, Anxiety, and Spatial Memory on Young Male Wistar Rats.
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.
1 Department of Anatomy, Faculty of Medicine, University of Porto , Porto, Portugal .|2 Center of Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto , Porto, Portugal .
Armando
A
Cardoso
1 Department of Anatomy, Faculty of Medicine, University of Porto , Porto, Portugal .
Sara
S
Magano
1 Department of Anatomy, Faculty of Medicine, University of Porto , Porto, Portugal .
Francisco
F
Marrana
1 Department of Anatomy, Faculty of Medicine, University of Porto , Porto, Portugal .|2 Center of Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto , Porto, Portugal .
José P
JP
Andrade
D000375:Aging / Q000187:drug effects*; D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001835:Body Weight / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology; D004032:Diet; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005690:Galactose / Q000008:administration & dosage / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects*
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D002392:Catechin; C045651:epigallocatechin gallate; D005690:Galactose