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Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients
Author(s) -
Dutta Ranjan,
Chang Ansi,
Doud Mary K.,
Kidd Grahame J.,
Ribaudo Michael V.,
Young Elizabeth A.,
Fox Robert J.,
Staugaitis Susan M.,
Trapp Bruce D.
Publication year - 2011
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.22337
Subject(s) - multiple sclerosis , neuroscience , amyotrophic lateral sclerosis , glutamate receptor , demyelinating disorder , synaptic plasticity , neurotransmission , hippocampal formation , central nervous system , medicine , biology , disease , pathology , immunology , receptor
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. Ann Neurol 2011;69:445–454