Persistent activation of microglia and NADPH oxidase [corrected] drive hippocampal dysfunction in experimental multiple sclerosis

Scientific Reports
Massimiliano Di FilippoPaolo Calabresi

Abstract

Cognitive impairment is common in multiple sclerosis (MS). Unfortunately, the synaptic and molecular mechanisms underlying MS-associated cognitive dysfunction are largely unknown. We explored the presence and the underlying mechanism of cognitive and synaptic hippocampal dysfunction during the remission phase of experimental MS. Experiments were performed in a chronic-relapsing experimental autoimmune encephalomyelitis (EAE) model of MS, after the resolution of motor deficits. Immunohistochemistry and patch-clamp recordings were performed in the CA1 hippocampal area. The hole-board was utilized as cognitive/behavioural test. In the remission phase of experimental MS, hippocampal microglial cells showed signs of activation, CA1 hippocampal synapses presented an impaired long-term potentiation (LTP) and an alteration of spatial tests became evident. The activation of hippocampal microglia mediated synaptic and cognitive/behavioural alterations during EAE. Specifically, LTP blockade was found to be caused by the reactive oxygen species (ROS)-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We suggest that in the remission phase of experimental MS microglia remains activated, causing synaptic dysfunctio...Continue Reading

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Citations

Aug 25, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Pallavi MadhusudananSahadev A Shankarappa
Jul 25, 2017·Multiple Sclerosis : Clinical and Laboratory Research·Mario Stampanoni BassiDiego Centonze
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Aug 14, 2020·Neural Regeneration Research·Lorenzo GaetaniMassimiliano Di Filippo
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Sep 26, 2020·Frontiers in Cellular Neuroscience·Melanie J PlastiniRoberta Brambilla
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Dec 12, 2018·Neural Regeneration Research·Andrea ManciniMassimiliano Di Filippo
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Aug 7, 2021·Biomolecules·Ilias Kalafatakis, Domna Karagogeos
Aug 26, 2021·Current Protocols·Raffaele d'IsaLetizia Leocani

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Methods Mentioned

BETA
infrared microscopy

Software Mentioned

Bioplex Manager
NIH ImageJ
image J

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