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.

Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis

“…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, ).…”

Resistance to experimental autoimmune encephalomyelitis development in Lewis rats from a conventional animal facility

“…The clinical course of MBP-induced EAE in the Lewis rat is an acute ascending paralysis, that is monophasic and self-limiting, making it an ideal model to study the regulatory events that lead to recovery from autoimmune diseases (Swanborg 1995). MS and EAE development are clearly affected by different factors as gender (Papenfuss et al 2004), age (Ditamo et al 2005), and also by genetic and environmental conditions (Sotgiu et al 2004). The hygiene hypothesis has been proposed to explain the increased incidence of autoimmune diseases and allergy in areas of the world with improved health care and sanitation.…”