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Muscarinic M1 receptors modulate endotoxemia-induced loss of synaptic plasticity

Aleksandar R Zivkovic1, Oliver Sedlaczek2, Rebecca von Haken3

  • 1Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. aleksandar.zivkovic@med.uni-heidelberg.de.

Acta Neuropathologica Communications
|November 5, 2015
PubMed

Insights

Septic encephalopathy impairs brain function, affecting synaptic plasticity in the hippocampus. Targeting small conductance calcium-activated potassium (SK) channels or boosting cholinergic activity may treat this condition.

Area of Science:

  • Neuroscience
  • Pathophysiology
  • Pharmacology

Background:

  • Septic encephalopathy causes rapid cortical dysfunction.
  • Magnetic resonance imaging (MRI) revealed hippocampal abnormalities in patients with septic delirium.
  • An animal model was used to investigate hippocampal dysfunction during sepsis.

Purpose of the Study:

  • To investigate the mechanisms underlying hippocampal dysfunction in sepsis.
  • To explore potential therapeutic targets for septic encephalopathy.

Main Methods:

  • Induction of endotoxemia in rats using lipopolysaccharide (LPS) injections.
  • Electrophysiological recordings in brain slices to assess synaptic plasticity.
  • Assessment of long-term potentiation (LTP) deficits.

Main Results:

  • Endotoxemia induced a deficit in long-term potentiation (LTP).
  • Apamin, an SK channel blocker, completely reversed the LTP deficit.
  • Physostigmine (an acetylcholinesterase inhibitor) and TBPB (an M1 agonist) partly restored LTP.

Conclusions:

  • Small conductance calcium-activated potassium (SK) channels play a role in endotoxemia-induced synaptic dysfunction.
  • Enhancing cholinergic function or M1 receptor activity can restore synaptic plasticity deficits.
  • Pharmacological interventions targeting SK channels or cholinergic pathways may treat septic delirium.

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