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Testosterone Restores Brain Function in Old Male Rats

The mitochondrial results mirror the behavioral results of this experiment.

Rat in mazeRat in maze

Researchers from Hebei Medical University in China have found that testosterone supplementation ameliorates age-related brain dysfunction in male rats.

A focus on mitochondria

Previous research has shown that testosterone supplementation helps offset some of the symptoms of Alzheimer’s disease [1] and Parkinson’s disease [2] in men. Although one study of castrated rats showed that their mitochondrial function was harmed and oxidative damage was increased [3], there has been no previous research examining the relationship between testosterone, mitochondria, and brain dysfunction.

Testosterone affects the fundamentals of cognition

The researchers used three groups of male rats in their experiment. One group was 6 months old, a second group was 24 months old and naturally had an average testosterone level one-third that of the 6-month-old rats, and the third group was 24 months old but were given testosterone supplements, which raised their average level slightly higher than that of the younger rats.

The behavioral effects were clear. Rats allowed to explore a chamber were tested for walking, climbing, rearing, and sniffing, and all four of these behaviors dramatically declined in older rats. Older rats given testosterone had their climbing, rearing, and sniffing behaviors partially restored, roughly to halfway between the results seen in younger rats and untreated older rats.

These sorts of behaviors are controlled by two primary brain regions: the substantia nigra and the hippocampus. In order to assess neuronal function, the researchers tested the expression of two brain chemicals, tyrosine hydroxylase and dopamine transporter, in these regions. These chemicals were partially restored in the rats given testosterone, and their chemical restoration strongly resembles their behavioral restoration. Neuronal integrity was also shown to be largely restored.

The mitochondrial results

The researchers then looked deeper to determine what testosterone was doing to mitochondria, examining both mitochondrial membrane potential and mitochondrial respiratory complex activities. These results largely mirrored what was seen in the other tests, although mitochondrial membrane potential was only slightly increased while many of the mitochondrial respiratory complex activities were substantially increased.

Antioxidant activities were also examined, as well as mitochondrial biogenesis and mitochondrial content, with very similar results among nearly all of the measurements. Once again, the older rats given testosterone were roughly at the midway point between younger rats and their untreated counterparts.

Taken together, these results show a strong link between mitochondrial dysfunction, testosterone depletion, and cognitive decline in older rats.


While these results are very conclusive, this is still a rat study, and the effects of supplemental testosterone in human beings may not be nearly as substantial. However, these findings do provide significant evidence for the idea that age-related testosterone loss may strongly contribute to mitochondria-related brain dysfunction in older people.

In addition to suggesting that testosterone supplementation may be beneficial, these results also provide evidence for the idea that treatments that are known to decrease testosterone may possibly be dangerous to brain integrity and function in older men.

One thing is very clear: the effects of testosterone on the neuronal mitochondria of older men are worth investigating with a clinical trial.

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[1] Beauchet, O. (2006). Testosterone and cognitive function: current clinical evidence of a relationship. European journal of endocrinology, 155(6), 773-781.

[2] Mitchell E, Thomas D, Burnet R. (2006). Testosterone improves motor function in Parkinson’s disease. J Clin Neurosci, 13:133–36.

[3] Hioki, T., Suzuki, S., Morimoto, M., Masaki, T., Tozawa, R., Morita, S., & Horiguchi, T. (2014). Brain testosterone deficiency leads to down-regulation of mitochondrial gene expression in rat hippocampus accompanied by a decline in peroxisome proliferator-activated receptor-? coactivator 1a expression. Journal of Molecular Neuroscience, 52(4), 531-537.

About the author
Josh Conway

Josh Conway

Josh is a professional editor and is responsible for editing our articles before they become available to the public as well as moderating our Discord server. He is also a programmer, long-time supporter of anti-aging medicine, and avid player of the strange game called “real life.” Living in the center of the northern prairie, Josh enjoys long bike rides before the blizzards hit.
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