Lipids shape brain function through ion channel and receptor modulations: physiological mechanisms and clinical perspectives

Physiol Rev. 2025 Jan 1;105(1):137-207. doi: 10.1152/physrev.00004.2024. Epub 2024 Jul 11.

Abstract

Lipids represent the most abundant molecular type in the brain, with a fat content of ∼60% of the dry brain weight in humans. Despite this fact, little attention has been paid to circumscribe the dynamic role of lipids in brain function and disease. Membrane lipids such as cholesterol, phosphoinositide, sphingolipids, arachidonic acid, and endocannabinoids finely regulate both synaptic receptors and ion channels that ensure critical neural functions. After a brief introduction on brain lipids and their respective properties, we review here their role in regulating synaptic function and ion channel activity, action potential propagation, neuronal development, and functional plasticity and their contribution in the development of neurological and neuropsychiatric diseases. We also provide possible directions for future research on lipid function in brain plasticity and diseases.

Keywords: brain diseased; ion channels; lipids; synaptic and intrinsic plasticity; synaptic receptors.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain* / metabolism
  • Brain* / physiology
  • Humans
  • Ion Channels* / metabolism
  • Ion Channels* / physiology
  • Neuronal Plasticity / physiology

Substances

  • Ion Channels