title: Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, OH 44195, USA.
authors: Ranjan
authors: R
authors: Dutta
authors: Ansi
authors: A
authors: Chang
authors: Mary K
authors: MK
authors: Doud
authors: Grahame J
authors: GJ
authors: Kidd
authors: Michael V
authors: MV
authors: Ribaudo
authors: Elizabeth A
authors: EA
authors: Young
authors: Robert J
authors: RJ
authors: Fox
authors: Susan M
authors: SM
authors: Staugaitis
authors: Bruce D
authors: BD
authors: Trapp
mesh_terms: D001370:Axonal Transport / Q000502:physiology; D001369:Axons / Q000473:pathology* / Q000502:physiology; D015153:Blotting, Western; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008568:Memory / Q000502:physiology; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009186:Myelin Sheath / Q000473:pathology* / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000473:pathology* / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000473:pathology* / Q000502:physiology; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D017470:Receptors, Glutamate; D050496:Vesicular Glutamate Transport Proteins