Age-related changes in the development of experimental autoimmune encephalomyelitis

Abstract

A prominent feature of multiple sclerosis is its high incidence of onset in the third decade of life and its relatively rare onset in persons older than 50 years. In order to study age-related restriction of clinical expression, a comparative biochemical, immunological and histological study was undertaken during development of experimental autoimmune encephalomyelitis (EAE) in young (7 weeks) and middle-aged (15 months) Wistar rats. Young rats showed characteristic clinical signs 12-16 days postinduction, and then they spontaneously recuperated. In middle-aged rats, the incidence of clinical signs was significantly reduced, with a later onset of the disease. Similar biochemical and histological alterations were detected in both age groups, but they were present in a later stage in middle-aged animals. However, cellular and humoral immune responses to myelin basic protein (MBP) were observed 15 days postinduction in all EAE animals. The study of anti-MBP IgG isotype pattern in 7-week-old animals indicated a predominant Th1-type immune response during the acute stage of EAE, with antibodies predominantly recognizing the MBP 96-128 peptide. In contrast, 15-month-old animals showed a less prominent Th1 response, without any epitope dominance. The changes in immune function found in middle-aged animals may account for the different susceptibility and expression of EAE, and may also be relevant to the different clinical expression observed in multiple sclerosis with maturation.

Murine Autoimmune Optic Neuritis Is Not Phenotypically Altered by the Retinal Degeneration 8 Mutation

“…2 AON, in common with most models of EAE, is induced in female mice of approximately 8 weeks of age because older mice are less susceptible to disease induction. 33,34 In this study, mice were approximately 14 weeks of age at the end of the experiment. At a similar age, mice homozygous for the rd8 mutation have been reported to have spot-like fundus abnormalities and alterations in retinal layering, photoreceptor degeneration, and Müller glia activation and an increase in subretinal microglia.…”

“…This is reflected in the absence of functional disturbances in photoreceptor and bipolar cells as demonstrated by ERGs. Although the pathology of the rd8 mutation has been reported to be progressive in nature and to be more severe in mice aged 10 months and older, 4,31,35 the susceptibility of animals to EAE induction is vastly reduced in animals more than 1 year old 33,34 ; thus we restricted our analysis to that of younger mice (3-4 months old).…”

Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis

“…however, it proves to be encephalitogenic in C57BL/6 mice (Delarasse, Smith, Baker, & Amor, 2013). Young C57BL/6 mice develop an acute monophasic form of EAE, whereas middle-aged males developed severe chronic EAE (Ditamo, Degano, Maccio, Pistoresi-Palencia, & Roth, 2005;Matejuk, Hopke, Vandenbark, Hurn, & Offner, 2005).…”

“…MOG is expressed at relatively low levels on the surface of myelin sheaths; however, it proves to be encephalitogenic in C57BL/6 mice (Delarasse, Smith, Baker, & Amor, ). Young C57BL/6 mice develop an acute monophasic form of EAE, whereas middle‐aged males developed severe chronic EAE (Ditamo, Degano, Maccio, Pistoresi‐Palencia, & Roth, ; Matejuk, Hopke, Vandenbark, Hurn, & Offner, ). Administration of pertussis is required for disease induction with MOG 35–55 /CFA in C57BL/6 mice, which develop a self‐limited monophasic disease (Bittner, Afzali, Wiendl, & Meuth, ; Schreiner, Heppner, & Becher, ).…”

In vivo immunomodulatory effect of the lectin from edible mushroom Agaricus bisporus

“…24 Starting one week before immunization and through the end of the experiment, one group of animals were orally administered with 80 µg per kg per day of ABL in sucrose and the control group received mock treatment. 24 Starting one week before immunization and through the end of the experiment, one group of animals were orally administered with 80 µg per kg per day of ABL in sucrose and the control group received mock treatment.…”