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Increased phosphorylation of mTOR is involved in remote ischemic preconditioning of hippocampus in mice

Fatemeh Zare Mehrjerdi1, Nahid Aboutaleb, Rouhollah Habibey

  • 1Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.

Brain Research
|June 29, 2013
PubMed

Insights

Remote ischemic preconditioning (RIPC) protects the hippocampus from injury by activating the mammalian target of rapamycin (mTOR) pathway. Inhibiting mTOR with rapamycin blocks these protective effects, highlighting mTOR

Area of Science:

  • Neuroscience
  • Cardiovascular Biology
  • Molecular Biology

Background:

  • Ischemia reperfusion (IR) injury affects tissues, with signaling pathways like mammalian target of rapamycin (mTOR) being crucial for protection.
  • Remote ischemic preconditioning (RIPC) offers a protective strategy against IR injury, but its specific mechanisms in the hippocampus require further elucidation.

Purpose of the Study:

  • To investigate the role of the mTOR pathway in mediating the neuroprotective effects of RIPC in the hippocampus against global brain ischemia.
  • To determine if inhibiting mTOR can abolish the beneficial outcomes of RIPC on hippocampal function and survival.

Main Methods:

  • Mice underwent renal IR to induce RIPC 24 hours before global brain ischemia.
  • Mice were treated with saline or rapamycin (an mTOR inhibitor) prior to RIPC.
  • Evaluated were mTOR/phosphorylated mTOR (p-mTOR) expression, superoxide dismutase (SOD) activity, memory retention, apoptosis, and neuronal cell density post-ischemia.

Main Results:

  • RIPC significantly reduced apoptosis and improved memory retention compared to IR alone.
  • RIPC also increased p-mTOR expression and SOD activity in the hippocampus.
  • Rapamycin treatment completely abolished the protective effects of RIPC, including reduced apoptosis and improved memory.

Conclusions:

  • The mammalian target of rapamycin (mTOR) pathway plays a critical role in mediating the neuroprotective effects of remote ischemic preconditioning (RIPC) in the hippocampus.
  • Targeting the mTOR pathway could be a potential therapeutic strategy for mitigating ischemia reperfusion injury in the brain.
Keywords:
ATP sensitive potassium channelsApoptosisCCACommon carotid arteryIRIschemia reperfusionKATPMAPKMammalian target of rapamycinMemoryMitochondrial ATP sensitive potassium channelsMitogen activated protein kinasesPATPassive avoidance testRIPCROSRapaRapamycinReactive Oxygen SpeciesRemote ischemia preconditioningRemote ischemic preconditioningSODSuperoxide dismutasemKATPmTOR

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