title: Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis.
abstract: A prominent clinical symptom in multiple sclerosis (MS), a progressive disorder of the central nervous system (CNS) due to heightened neuro-inflammation, is learning and memory dysfunction. Here, we investigated the effects of a ketogenic diet (KD) on memory impairment and CNS-inflammation in a murine model of experimental autoimmune encephalomyelitis (EAE), using electrophysiological, behavioral, biochemical and in vivo imaging approaches. Behavioral spatial learning deficits were associated with motor disability in EAE mice, and were observed concurrently with brain inflammation. The KD improved motor disability in the EAE model, as well as CA1 hippocampal synaptic plasticity (long-term potentiation) and spatial learning and memory (assessed with the Morris Water Maze). Moreover, hippocampal atrophy and periventricular lesions in EAE mice were reversed in KD-treated EAE mice. Finally, we found that the increased expression of inflammatory cytokines and chemokines, as well as the production of reactive oxygen species (ROS), in our EAE model were both suppressed by the KD. Collectively, our findings indicate that brain inflammation in EAE mice is associated with impaired spatial learning and memory function, and that KD treatment can exert protective effects, likely via attenuation of the robust immune response and increased oxidative stress seen in these animals.
authors.affiliation: Barrow Neurological Institute, Medical Center, St. Joseph's Hospital, Phoenix, Arizona, United States of America.
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Junwei
authors.initials: J
authors.lastname: Hao
authors.forename: Ruolan
authors.initials: R
authors.lastname: Liu
authors.forename: Gregory
authors.initials: G
authors.lastname: Turner
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
authors.forename: Jong M
authors.initials: JM
authors.lastname: Rho
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002490:Central Nervous System / Q000473:pathology; D004594:Electrophysiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008569:Memory Disorders / Q000276:immunology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species