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.
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 MSpatients demonstrate memory impairment. The molecular basis of this memory dysfunction has not yet been investigated in MSpatients. METHODS: To investigate possible mechanisms of memory impairment in MSpatients, 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 MSpatients and establish that the neuronal genes regulated by myelination reflect specific functions of neuronal subpopulations.
Authors: Eric M Blalock; James W Geddes; Kuey Chu Chen; Nada M Porter; William R Markesbery; Philip W Landfield Journal: Proc Natl Acad Sci U S A Date: 2004-02-09 Impact factor: 11.205
Authors: V Mack; N Burnashev; K M Kaiser; A Rozov; V Jensen; O Hvalby; P H Seeburg; B Sakmann; R Sprengel Journal: Science Date: 2001-06-29 Impact factor: 47.728
Authors: Stephanie B Syc; Shiv Saidha; Scott D Newsome; John N Ratchford; Michael Levy; E'tona Ford; Ciprian M Crainiceanu; Mary K Durbin; Jonathan D Oakley; Scott A Meyer; Elliot M Frohman; Peter A Calabresi Journal: Brain Date: 2011-10-17 Impact factor: 13.501
Authors: Pavan Bhargava; Carlos Nogueras-Ortiz; Sol Kim; Francheska Delgado-Peraza; Peter A Calabresi; Dimitrios Kapogiannis Journal: Mult Scler Date: 2020-06-17 Impact factor: 6.312
Authors: Stefan M Gold; Mary-Frances O'Connor; Raja Gill; Kyle C Kern; Yonggang Shi; Roland G Henry; Daniel Pelletier; David C Mohr; Nancy L Sicotte Journal: Hum Brain Mapp Date: 2012-07-30 Impact factor: 5.038