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Metformin Plus Caloric Restriction Show Anti-epileptic Effects Mediated by mTOR Pathway Inhibition

María Del Carmen Rubio Osornio1, Verónica Custodio Ramírez1, Daniela Calderón Gámez2

  • 1Laboratorio de Neurofisiología, Instituto Nacional de Neurología y Neurocirugía, Av. Insurgentes Sur 3877, Col. La Fama, Del. Tlalpan, 14269, Mexico City, Mexico.

Cellular and Molecular Neurobiology
|August 23, 2018
PubMed

Insights

Caloric restriction combined with metformin shows anti-epileptic effects by inhibiting the mTOR pathway. This combination therapy is promising for patients with generalized convulsive seizures, particularly those who are overweight or have metabolic syndrome.

Area of Science:

  • Neuroscience
  • Metabolic Disorders

Background:

  • Caloric restriction (CR) demonstrates anti-epileptic properties, partly by inhibiting the mechanistic/mammalian target of rapamycin (mTOR) pathway.
  • Adenosine monophosphate-activated protein kinase (AMPK) activation, triggered by low energy levels, inhibits mTOR signaling.

Purpose of the Study:

  • To investigate the effects of metformin, alone and in combination with CR, on an electrical kindling epilepsy model.
  • To examine the impact on the mTOR cascade in the hippocampus and neocortex.

Main Methods:

  • Utilized an electrical kindling epilepsy model in animals.
  • Administered metformin and caloric restriction, both individually and in combination.
  • Analyzed mTOR signaling pathway activity in hippocampal and neocortical tissues.

Main Results:

  • The combination of metformin and CR significantly improved various aspects of kindling, particularly reducing generalized convulsive seizures.
  • Metformin and CR demonstrated a combined beneficial effect on seizure measures.

Conclusions:

  • Metformin combined with caloric restriction may reduce epileptic activity in patients experiencing generalized convulsive seizures.
  • Obese or overweight patients with epilepsy and metabolic syndrome are ideal candidates for clinical trials evaluating this combined therapy.
Keywords:
Caloric restrictionElectrical kindlingEpilepsyMetforminmTOR signaling pathway

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