Dietary restriction (DR) – restricting some or all nutrients in the diet, without causing malnutrition – is known to reduce some effects of ageing and increase longevity. A new study shows that – for roundworms, at least – it also enhances the ability to learn.
In a study published in PLOS Biology, Mihir Vohra, Kaveh Ashrafi and colleagues at the University of California, San Francisco suggest that DR enhances the ability to learn by limiting the production of a metabolite known as kynurenic acid (KYNA). KYNA acts as an antagonist to a vital neurotransmitter involved in learning called glutamate; when KYNA production is limited, the signaling that occurs during learning can occur more easily.
Prior to this study, an association between DR, insulin signaling and improved learning and lifespan had been found – but the underlying mechanisms remained unclear.
Vohra and Ashrafi were determined to investigate. Using C. elegans roundworms, they performed what is called a ‘butatone association assay’. Butatone is odorous chemical that animals generally find offensive, but they can be conditioned to like it. This conditioning is then used as an indicator of their learning ability.
The roundworms were put on a restricted diet and underwent genetic and pharmaceutical interventions that altered pathways associated with the physiological responses to DR. They were then conditioned to be attracted to butatone.
It was found that for all interventions, C. elegans learning improved, but lifespan remained the same. Molecular investigation showed that due to DR there was a decrease in a specific enzyme needed to produce KYNA, this limiting its ability to block glutamate signaling and allowing learning to occur at a faster rate.
The significance of the result may not be limited to roundworms, as mammals use KYNA in a similar way. Also, the KYNA pathway has been associated with many human neurodegenerative disorders, meaning this study may give us insight into new therapeutic treatments.
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