Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients
- 19 November 2010
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 69 (3), 445-454
- https://doi.org/10.1002/ana.22337
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. 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;69:445–454This publication has 34 references indexed in Scilit:
- New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?Nature Reviews Neuroscience, 2010
- A New Component in Synaptic Plasticity: Upregulation of Kinesin in the Neurons of the Gill-Withdrawal ReflexCell, 2008
- Understanding Synapses: Past, Present, and FutureNeuron, 2008
- Neuroligins and neurexins link synaptic function to cognitive diseaseNature, 2008
- Calmodulin-Kinases: Modulators of Neuronal Development and PlasticityNeuron, 2008
- Neurogenesis in the chronic lesions of multiple sclerosisBrain, 2008
- Common molecular mechanisms in explicit and implicit memoryJournal of Neurochemistry, 2006
- Cognitive dysfunction in multiple sclerosis: a review of recent developmentsCurrent Opinion in Neurology, 2003
- Kinectin, an Essential Anchor for Kinesin-Driven Vesicle MotilityScience, 1995
- On the nature of memory disturbance in multiple sclerosisJournal of Clinical and Experimental Neuropsychology, 1989