D-galactose-induced brain ageing model: A systematic review and meta-analysis on cognitive outcomes and oxidative stress indices

Abstract

Animal models are commonly used in brain ageing research. Amongst these, models where rodents are exposed to d-galactose are held to recapitulate a number of features of ageing including neurobehavioral and neurochemical changes. However, results from animal studies are often inconsistent. To better understand the characteristics of the model and effects of d-galactose on neurobehavioral and neurochemical outcomes in rodents we performed a systematic review and meta-analysis. We applied random-effects meta-analysis to evaluate the effect of study features. Our results give an overview of the characteristics of the dgalactose rodent ageing model, including neurobehavioral and neurochemical outcomes. We found that few studies took measures to reduce risks of bias, and substantial heterogeneity in the reported effects of d-galactose in included studies. This highlights the need for improvements in the use of the d-galactose rodent ageing model if it is to provide useful in the development of drugs to treat human ageing.

Plasma metabolites related to cellular energy metabolism are altered in adults with Down syndrome and Alzheimer's disease

“…It is thus possible that membrane lipid synthesis and glycolysis may compete for uridine under circumstances when glucose is unabundant relative to other, alternative carbohydrate sources such as galactose. It is interesting to note that the administration of supra-physiological doses of D-galactose to rodents is a potent, accepted model of accelerated aging (Sadigh-Eteghad et al, 2017). Although this has mechanistically been understood to result from the formation of toxic advanced glycation end products (AGEs) and consequent oxidative stress (Davis, Prasad, Vijayagopal, Juma, & Imrhan, 2016;Maessen, Stehouwer, & Schalkwijk, 2015;Odetti et al, 1998), it may also be consequent to D-galactose's effects on bioenergetic tone and its dependence on UDP-glucose as a metabolic cofactor.…”

Bungeanum Improves Cognitive Dysfunction and Neurological Deficits in D-Galactose-Induced Aging Mice via Activating PI3K/Akt/Nrf2 Signaling Pathway

“…Thus, preventing oxidative stress-induced neuronal degeneration might be crucial to prevent the aging process and its associated neurodegenerative diseases such as Alzheimer's disease (AD). D-galactose is a physiological nutrient that is involved in glucose metabolism, but its excessive accumulation produces redundant ROS formation and decreases endogenous antioxidant enzyme activity, cognitive dysfunction, and neurological deficits in rodents (Hao et al, 2014;Sadigheteghad et al, 2017). Consequently, D-galactose-induced aging mice were used to mimic aging brain pathology in this present study.…”

Advance of sporadic Alzheimer's disease animal models

“…D ‐gal‐induced AD animal models are suitable for the research related to the pathogenesis of AD in aging. Meanwhile, the models do not show typical AD pathological features, such as Aβ deposition, NFTs formation, and neuronal apoptosis …”

“…Meanwhile, the models do not show typical AD pathological features, such as Aβ deposition, NFTs formation, and neuronal apoptosis. 77 What is worth to mention is that gender may be a key point for developing the D-gal induced AD models.…”