Antioxidants Rescue Cognitive Decline in Mice

#1

I’m always a little skeptical of “mouse models” of diseases… as we’ve seen in Alzheimers the models are frequently not very good. Does anyone know anything about this mouse model of cognitive decline? @Olafurpall

The researchers used a mouse model of age-related cognitive decline induced by D-galactose (D-gal), a compound that exacerbates oxidative stress. D-gal-treated animals exhibit numerous symptoms of aging, including mitochondrial dysfunction, inflammation, and neuronal degeneration, highlighting the broad range of ROS’ effects.

Previous studies have shown that both curcumin and EGCG improve memory function in aged mice, at least partially via antioxidative pathways. However, the results of a very limited number of existing studies that considered the cumulative effects of those two molecules were inconclusive.

The researchers ran a battery of behavioral tests on several groups of mice, such as the passive avoidance task, which capitalizes on a rodent’s natural preference for darkness and its ability to learn to avoid an environment in which it has experienced an aversive stimulus. In this test, naturally aged and D-gal-treated mice showed less retention time and lower rate of freezing response, which is indicative of poorer memory.

Related Papers:

[1] Rahman, M. A., Shuvo, A. A., Apu, M. M. H., Bhakta, M. R., Islam, F., Rahman, M. A., … & Reza, H. M. (2023). Combination of epigallocatechin 3 gallate and curcumin improves d-galactose and normal-aging associated memory impairment in mice. Scientific Reports, 13(1), 12681.

https://www.nature.com/articles/s41598-023-39919-4

[2] Kim, G. H., Kim, J. E., Rhie, S. J., & Yoon, S. (2015). The role of oxidative stress in neurodegenerative diseases. Experimental neurobiology, 24(4), 325.

[3] Nagle, D. G., Ferreira, D., & Zhou, Y. D. (2006). Epigallocatechin-3-gallate (EGCG): chemical and biomedical perspectives. Phytochemistry, 67(17), 1849-1855.

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I’m not a fan of the D-galactose mouse model. I don’t take studies on it very seriously. It’s basically a model that results in increased oxidative stress and damage that causes features somewhat similar to those caused by aging. If they then use antioxidants like EGCG in mice given D-gal, then the EGCG is mainly preventing the damage D-gal would cause. Therefore EGCG is likely mostly preventing the harm caused by D-gal rather than necessarily preventing or slowing down natural aging. The benefit of EGCG during such excessive oxidative stress doesn’t mean it will be of benefit in normal conditions. It’s a bit similar to giving obese mice something that causes weight loss or improves their insulin sensitivity and increases their lifespan by doing so. That doesn’t mean the same treatment will improve the health of mice that aren’t obese or insulin resistant in the first place. So I take studies on D-gal mice with a grain of salt.

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