Journal Article

Inflammation-Mediated Memory Dysfunction and Effects of a Ketogenic Diet in a Murine Model of Multiple Sclerosis

Kim, Do Young, Liu, Ruolan, Rho, Jong M., Hao, Junwei, Shi, Fu-Dong, Turner, Gregory

2012

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Alternative medicine / Animal models / Animals / Atrophy / Behavioral plasticity / Biology / Biosynthesis / Brain / Brain - immunology / Brain - metabolism / Brain - pathology / Carbohydrates / Central nervous system / Central Nervous System - pathology / Chemokines / Convulsions & seizures / Cytokines / Diet / Electrophysiology / Encephalomyelitis, Autoimmune, Experimental - metabolism / Encephalomyelitis, Autoimmune, Experimental - pathology / Experimental allergic encephalomyelitis / Fatty acids / Flow Cytometry / Gangrene / High fat diet / Hippocampal plasticity / Hippocampus / Hospitals / Hypoxia / Immune response / Immune system / Immunology / Inflammation / Inflammation - metabolism / Inflammation - pathology / Inflammation - physiopathology / Ketogenesis / Lesions / Long-term potentiation / Long-Term Potentiation - physiology / Low carbohydrate diet / Magnetic Resonance Imaging / Maze learning / Medicine / Memory / Memory Disorders - immunology / Memory Disorders - physiopathology / Mice / Mice, Inbred C57BL / Multiple sclerosis / Multiple Sclerosis - immunology / Multiple Sclerosis - metabolism / Multiple Sclerosis - pathology / Neuroimaging / NMR / Nuclear magnetic resonance / Oxidative stress / Oxygen / Plasticity (synaptic) / Proteins / Reactive oxygen species / Reactive Oxygen Species - metabolism / Rodents / Shinto / Social and Behavioral Sciences / Spatial discrimination learning / Spatial memory / Synaptic plasticity