Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients
Annals of neurology, 2011•Wiley Online Library
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 …
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 …
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
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