Platelet-Activating Factor Receptors Mediate Excitatory Postsynaptic Hippocampal Injury in Experimental Autoimmune Encephalomyelitis

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Matthew J BellizziHarris A Gelbard

Abstract

Gray matter degeneration contributes to progressive disability in multiple sclerosis (MS) and can occur out of proportion to measures of white matter disease. Although white matter pathology, including demyelination and axon injury, can lead to secondary gray matter changes, we hypothesized that neurons can undergo direct excitatory injury within the gray matter independent of these. We tested this using a model of experimental autoimmune encephalomyelitis (EAE) with hippocampal degeneration in C57BL/6 mice, in which immunofluorescent staining showed a 28% loss of PSD95-positive excitatory postsynaptic puncta in hippocampal area CA1 compared with sham-immunized controls, despite preservation of myelin and VGLUT1-positive excitatory axon terminals. Loss of postsynaptic structures was accompanied by appearance of PSD95-positive debris that colocalized with the processes of activated microglia at 25 d after immunization, and clearance of debris was followed by persistently reduced synaptic density at 55 d. In vitro, addition of activated BV2 microglial cells to hippocampal cultures increased neuronal vulnerability to excitotoxic dendritic damage following a burst of synaptic activity in a manner dependent on platelet-activating fa...Continue Reading

Citations

Dec 11, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ronan LordanConstantinos A Demopoulos
Jul 14, 2020·Frontiers in Cellular Neuroscience·Antonio BrunoGeorgia Mandolesi
Nov 27, 2020·Journal of Neuroinflammation·Nicole D Schartz, Andrea J Tenner
Mar 11, 2020·Brain, Behavior, and Immunity·Jennetta W HammondHarris A Gelbard
Feb 18, 2021·Trends in Immunology·Lucas SchirmerPeter A Calabresi
Mar 5, 2021·Frontiers in Neurology·Christian Wilson R TuraldeVeeda Michelle M Anlacan
Apr 3, 2021·Frontiers in Endocrinology·Jeffrey B TraversRavi P Sahu
Apr 18, 2021·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Chunrong LiKangding Liu
May 1, 2021·Cells·Jana Krystofova Mike, Donna Marie Ferriero
Jun 30, 2021·Neurochemistry International·Ivan A LindhoutAndis Klegeris

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