ketogenic diets neuronal excitability purine June 1, 2022

Purines are vital to many numerous mobile processes. The purine adenine is a nitrogenous base that in all likelihood performed a function in prebiotic evolution. Therefore, it isn’t unexpected that it’s far each a constructing block of DNA and RNA, reflecting the metabolic interest of cellular, in addition to an issue of the principle cellular power molecule, the adenine nucleotide adenosine triphosphate (ATP), reflecting the metabolic ability of a cellular. Thus ATP and its middle molecule adenosine adapt mobile interest to power homeostasis all through the body.

Adenosine’s presence all through the extracellular area exerts a tonic impact on valuable anxious device interest thru G-protein coupled receptors, and – because of its interrelationship with adenine nucleotides, consisting of ATP – adenosine is in a unique function to hyperlink metabolism and neuronal interest.

Adenosine is launched at some stage in mobile stress, consisting of at some stage in hypoxia, ischemia, and seizures. Its neuroprotective function at some stage in situations of excessive metabolic demand – wherein adenosine’s effective inhibitory impact can lessen excitability and decrease excitotoxicity – has earned adenosine popularity as a retaliatory metabolite. However, adenosine and ATP have additionally been proven to be regulated with the aid of using some non-pathological stimuli, inclusive of reduced pH and elevated temperature.

Ketogenic diet, Synaptic Plasticity and Adenosine

Adenosine interacts with synaptic plasticity, consisting of long-time period potentiation at hippocampal synapses.  The amplitude of the long-time period potentiation remained dwindled drastically within the ketogenic weight-reduction plan institution out to the longest recorded time, forty-eight hours. Non-tremendous consequences of the ketogenic weight-reduction plan on long-time period potentiation in vivo in previous electrophysiology look could have been because of using fashionable anesthesia, that could weigh down the slight inhibition produced with the aid of using a ketogenic weight-reduction plan. Overall, the consequences of a ketogenic weight-reduction plan on long-time period potentiation determined to date are minor – it became dwindled, now no longer abolished – and within the predicted path primarily based totally on a courting amongst a ketogenic weight-reduction plan, adenosine, and long-time period potentiation.

ATP and adenosine are purines that play twin roles in cellular metabolism and neuronal signaling. Acting on the A1 receptor (A1R) subtype, adenosine acts at once on neurons to inhibit excitability and is an effective endogenous neuroprotective and anticonvulsant molecule. Previous studies confirmed a boom in ATP and different cellular power parameters while an animal is run a ketogenic weight-reduction plan, an established metabolic remedy to lessen epileptic seizures, however, the courting amongst purines, neuronal excitability, and the ketogenic weight-reduction plan became unclear.


Data is gathering that purines play a key position within the anticonvulsant results of a ketogenic diet.  The connection among elevated mitochondria and strength molecules with a ketogenic diet, and former studies linking purines to epilepsy in general – e.g. the connection among ATP and seizures, and anticonvulsant results of adenosine – even in pharmacoresistant epilepsy is established.