Adiponectin targets the AMPK/mTOR signaling pathway to alleviate cognitive impairment in epilepsy

Mol Med Rep. 2025 Mar;31(3):64. doi: 10.3892/mmr.2025.13429. Epub 2025 Jan 3.

Abstract

Among patients with chronic epilepsy, 70‑80% have cognitive impairment. To investigate the relationship between adiponectin (ADPN) and the cognitive level in epilepsy and its mechanism, 20 epileptic patients and 20 healthy controls were included for the assessment of the cognitive level. An ELISA was used to evaluate the serum ADPN level. An epileptic rat model was established and treated with AdipoRon, an ADPN receptor (AdipoR) agonist, which binds to AdipoR1 and AdipoR2. The Morris water maze test was used to assess the cognitive function of rats, and the expression levels of the synapsis‑associated proteins postsynaptic density protein 95 (PSD95), synaptosomal associated protein 25 (SNAP25) and synaptophysin (SYP), as well as AMP‑activated protein kinase (AMPK), mTOR, phosphorylated (p‑)AMPK and p‑mTOR were determined by immunoblotting. Serum ADPN levels were positively correlated with the Montreal cognitive assessment score. AdipoRon improved the cognitive function of epileptic rats, maintained the structural integrity of hippocampal neurons and reduced neuronal damage. It also promoted the mRNA expression of AdipoR1 and AdipoR2 in the hippocampus. Furthermore, AdipoRon increased the expression of the synapsis‑associated proteins PSD95, SNAP25 and SYP by activating the AMPK/mTOR signaling pathway. ADPN improved cognitive impairment in epilepsy by targeting the AMPK/mTOR signaling pathway, providing novel insights for the treatment of epilepsy.

Keywords: ADPN; AMPK/mTOR pathway; AdipoRon; cognition disorders; epilepsy.

MeSH terms

  • AMP-Activated Protein Kinases* / metabolism
  • Adiponectin* / metabolism
  • Adult
  • Animals
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / metabolism
  • Disease Models, Animal
  • Epilepsy* / drug therapy
  • Epilepsy* / metabolism
  • Female
  • Hippocampus / metabolism
  • Humans
  • Male
  • Middle Aged
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adiponectin / metabolism
  • Signal Transduction*
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • TOR Serine-Threonine Kinases
  • Adiponectin
  • AMP-Activated Protein Kinases
  • Receptors, Adiponectin
  • MTOR protein, human