Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients

Ann Neurol. 2011 Mar;69(3):445-54. doi: 10.1002/ana.22337.


Objective: Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system. Although the clinical impact of gray matter pathology in MS brains is unknown, 30 to 40% of MS patients demonstrate memory impairment. The molecular basis of this memory dysfunction has not yet been investigated in MS patients.

Methods: To investigate possible mechanisms of memory impairment in MS patients, we compared morphological and molecular changes in myelinated and demyelinated hippocampi from postmortem MS brains.

Results: Demyelinated hippocampi had minimal neuronal loss but significant decreases in synaptic density. Neuronal proteins essential for axonal transport, synaptic plasticity, glutamate neurotransmission, glutamate homeostasis, and memory/learning were significantly decreased in demyelinated hippocampi, but not in demyelinated motor cortices from MS brains.

Interpretation: Collectively, these data support hippocampal demyelination as a cause of synaptic alterations in MS patients and establish that the neuronal genes regulated by myelination reflect specific functions of neuronal subpopulations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axonal Transport / physiology
  • Axons / pathology*
  • Axons / physiology
  • Blotting, Western
  • Gene Expression
  • Hippocampus / metabolism
  • Hippocampus / pathology*
  • Hippocampus / physiopathology
  • Humans
  • Memory / physiology
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / pathology*
  • Multiple Sclerosis / physiopathology
  • Myelin Sheath / pathology*
  • Myelin Sheath / physiology
  • Nerve Fibers, Myelinated / pathology*
  • Nerve Fibers, Myelinated / physiology
  • Neurons / pathology
  • Neurons / physiology
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Receptors, Glutamate / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synapses / pathology*
  • Synapses / physiology
  • Vesicular Glutamate Transport Proteins / metabolism


  • RNA, Messenger
  • Receptors, Glutamate
  • Vesicular Glutamate Transport Proteins