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author:("loud, Mary K")
1.  Hippocampal demyelination and memory dysfunction are associated with increased levels of the neuronal microRNA miR-124 and reduced AMPA receptors 
Annals of neurology  2013;73(5):637-645.
Background
Hippocampal demyelination, a common feature of postmortem multiple sclerosis (MS) brains, reduces neuronal gene expression and is a likely contributor to the memory impairment that is found in greater than 40% of individuals with (MS). How demyelination alters neuronal gene expression is unknown.
Methods
To explore if loss of hippocampal myelin alters expression of neuronal microRNAs (miRNA), we compared miRNA profiles from myelinated and demyelinated hippocampi from postmortem MS brains and performed validation studies.
Findings
A network-based interaction analysis depicts a correlation between increased neuronal miRNAs and decreased neuronal genes identified in our previous study. The neuronal miRNA miR-124, was increased in demyelinated MS hippocampi and targets mRNAs encoding 26 neuronal proteins that were decreased in demyelinated hippocampus, including the ionotrophic glutamate receptors, AMPA 2 and AMPA3. Hippocampal demyelination in mice also increased miR-124, reduced expression of AMPA receptors and decreased memory performance in water maze tests. Remyelination of the mouse hippocampus reversed these changes.
Conclusion
We establish here that myelin alters neuronal gene expression and function by modulating the levels of the neuronal miRNA miR-124. Inhibition of miR-124 in hippocampal neurons may provide a therapeutic approach to improve memory performance in MS patients.
doi:10.1002/ana.23860
PMCID: PMC3679350  PMID: 23595422
Multiple sclerosis; myelin; microRNA
2.  Demyelination Causes Synaptic Alterations in Hippocampi from Multiple Sclerosis Patients 
Annals of neurology  2011;69(3):445-454.
Background
Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system. While the clinical impact of gray matter pathology in MS brains is unknown, 30–40% of MS patients demonstrate memory impairment. The molecular basis of this memory dysfunction has not yet been investigated in MS patients.
Method
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.
Findings
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.
doi:10.1002/ana.22337
PMCID: PMC3073544  PMID: 21446020
Multiple Sclerosis; hippocampus; demyelination; memory

Results 1-2 (2)