Spontaneous Recurrent Seizures Mediated Cardiac Dysfunction via mTOR Pathway Upregulation: A Putative Target for

Supriya Sharma1,2, Arindam G Mazumder1,2, Anil K Rana1,2

  • 1Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur-176061, Himachal Pradesh, India.

Abstract

Insights

Sudden Unexpected Death in Epilepsy (SUDEP) involves cardiac dysfunction. This study found that mTOR pathway upregulation in epilepsy leads to heart problems, suggesting it as a target for SUDEP prevention.

Area of Science:

  • Neuroscience
  • Cardiology
  • Molecular Biology

Background:

  • Sudden Unexpected Death in Epilepsy (SUDEP) is a serious complication of epilepsy.
  • SUDEP is characterized by electrophysiological alterations leading to cardiac dysfunction and sudden death.

Purpose of the Study:

  • To investigate molecular and cardiac changes during epileptogenesis in a rat model.
  • To understand the mechanisms underlying cardiac dysfunction in epilepsy.

Main Methods:

  • Lithium-pilocarpine (Li-pilo) induced epilepsy in rats, creating Spontaneous Recurrent Seizures (SRS).
  • Cardiac function was assessed via blood pressure and ECG at different SRS phases (latent, initial, late).
  • Serum biochemistry, cardiac histology, and protein/mRNA expression (including mTOR pathway markers) were analyzed.

Main Results:

  • Epileptic rats showed altered blood pressure, cardiac hypertrophy, degeneration, and fibrosis.
  • Elevated serum markers (LDH, CK-MB) and increased cardiac expression of HIF-1α, mTOR, TGF-β, and ion channels were observed.
  • Upregulation of the mTOR pathway was a key finding in the cardiac tissue of epileptic animals.

Conclusions:

  • Epilepsy-induced Spontaneous Recurrent Seizures (SRS) cause cardiac dysfunction.
  • The mTOR pathway plays a crucial role in this cardiac dysfunction.
  • Targeting the mTOR pathway may offer a strategy for managing SUDEP.

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