AI Article Synopsis
- One-third of epilepsy patients do not respond to existing anti-seizure medications, prompting exploration of alternative treatments like the ketogenic diet.
- This study investigates the role of the hydroxycarboxylic acid receptor 2 (HCA2) in the diet's effectiveness, finding that HCA2 agonists can decrease seizures in animal models.
- The ketogenic diet boosts levels of natural HCA2 agonists, and the diet's anti-seizure effects were absent in mice lacking HCA2, indicating its potential as a target for epilepsy and possibly neurodegenerative diseases.
Article Abstract
One third of epilepsy patients are resistant to treatment with current anti-seizure medications. The ketogenic diet is used to treat some forms of refractory epilepsy, but the mechanism of its action has not yet been elucidated. In this study, we aimed to investigate whether the hydroxycarboxylic acid receptor 2 (HCA2), a known immunomodulatory receptor, plays a role in mediating the protective effect of this diet. We demonstrate for the first time that selective agonists at this receptor can directly reduce seizures in animal models. Agonists also reduce network activity in rodent and human brain slices. Ketogenic diet is known to increase circulating levels of endogenous HCA2 agonists, and we show that the effect of ketogenic diet in reducing seizures in the 6 Hz seizure model is negated in HCA2-deficient mice. Our data support the potential of HCA2 as a target for the treatment of epilepsy and potentially for neurodegenerative diseases.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496569 | PMC |
| http://dx.doi.org/10.1002/prp2.70026 | DOI Listing |
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