Maladaptive cortical hyperactivity upon recovery from experimental autoimmune encephalomyelitis

Autor: Erik Ellwardt, Zeke Barger, Johannes Vogt, Inigo Ruiz de Azua, Isabelle Arnoux, Beat Lutz, Tanja Kuhlmann, Eduardo Rosales Jubal, Christina F. Vogelaar, Tanja Novkovic, Gautam Pramanik, Melanie Schmalz, Frauke Zipp, Thomas Mittmann, Shibajee Mandal, Stefan Bittner, Dirk Luchtman, Albrecht Stroh
Rok vydání: 2017
Předmět:
0301 basic medicine
Encephalomyelitis
Autoimmune
Experimental
Encephalomyelitis
Freund's Adjuvant
Carbazoles
Mice
Transgenic
AMPA receptor
Tetrodotoxin
Hyperkinesis
Membrane Potentials
03 medical and health sciences
Cuprizone
Mice
0302 clinical medicine
Quinoxalines
medicine
Premovement neuronal activity
Animals
Myelin Proteolipid Protein
Egtazic Acid
Cells
Cultured
Cerebral Cortex
business.industry
General Neuroscience
Multiple sclerosis
Neurodegeneration
Experimental autoimmune encephalomyelitis
Anti-Inflammatory Agents
Non-Steroidal
Recovery of Function
medicine.disease
Peptide Fragments
Disease Models
Animal
030104 developmental biology
Synaptic plasticity
Excitatory postsynaptic potential
Female
Microglia
business
Neuroscience
Excitatory Amino Acid Antagonists
Proto-Oncogene Proteins c-fos
030217 neurology & neurosurgery
Sodium Channel Blockers
Zdroj: Nature neuroscience. 21(10)
ISSN: 1546-1726
Popis: Multiple sclerosis (MS) patients exhibit neuropsychological symptoms in early disease despite the immune attack occurring predominantly in white matter and spinal cord. It is unclear why neurodegeneration may start early in the disease and is prominent in later stages. We assessed cortical microcircuit activity by employing spiking-specific two-photon Ca2+ imaging in proteolipid protein-immunized relapsing-remitting SJL/J mice in vivo. We identified the emergence of hyperactive cortical neurons in remission only, independent of direct immune-mediated damage and paralleled by elevated anxiety. High levels of neuronal activity were accompanied by increased caspase-3 expression. Cortical TNFα expression was mainly increased by excitatory neurons in remission; blockade with intraventricular infliximab restored AMPA spontaneous excitatory postsynaptic current frequencies, completely recovered normal neuronal network activity patterns and alleviated elevated anxiety. This suggests a dysregulation of cortical networks attempting to achieve functional compensation by synaptic plasticity mechanisms, indicating a link between immune attack and early start of neurodegeneration.
Databáze: OpenAIRE
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