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Glial fibrillary acidic protein in chronic relapsing experimental allergic encephalomyelitis in SJL/J mice
1Department of Neurology, Veterans Administration Medical Center, Palo Alto, CA 94304.
Abstract:
The gliotic scar in the demyelinated plaque is a prominent feature of the pathology of multiple sclerosis. Chronic relapsing experimental allergic encephalomyelitis (EAE) in the SJL/J mouse has many characteristics in common with multiple sclerosis in the human, including the development of intense gliosis during the course of the demyelinating disease. With the use of antibody to the astrocyte marker glial fibrillary acidic protein (GFAP) we have measured the increase of GFAP over an 11-month course of chronic EAE. Intense staining of astrocyte fibers was seen around EAE lesions, which were most frequently observed in the cerebellum, periventricular areas, and in the spinal cord. The relative amount of GFAP was estimated by preparation of cytoskeletal proteins from the affected CNS areas, separation of proteins by polyacrylamide gel electrophoresis, and quantitation of GFAP in relation to the 70-kD neurofilament protein (NF) in gel scans. The ratio GFAP/70-kD NF protein in control animals did not change significantly over 11 months, whereas this ratio gradually increased to 2.54 in animals with chronic relapsing EAE 6 months after immunization. Although some decrease of neural fibers may have contributed partially to this change in ratio, the amounts of GFAP were greatly increased. These results indicate that the SJL/J mouse with chronic relapsing EAE provides an excellent model with which to investigate the formation and development of the gliotic plaque analogous to that seen in demyelinated areas in multiple sclerosis tissue.
Insights
Multiple sclerosis pathology involves gliotic scars. Chronic relapsing experimental allergic encephalomyelitis (EAE) in mice models this, showing increased glial fibrillary acidic protein (GFAP) indicating gliosis in demyelinated plaques.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Multiple sclerosis (MS) is characterized by demyelination and gliotic scarring in the central nervous system (CNS).
- Chronic relapsing experimental allergic encephalomyelitis (EAE) in SJL/J mice shares key pathological features with MS, including significant gliosis.
Purpose of the Study:
- To quantify the increase in glial fibrillary acidic protein (GFAP), an astrocyte marker, during an 11-month course of chronic EAE.
- To evaluate the SJL/J mouse model for studying gliotic plaque formation relevant to MS.
Main Methods:
- Antibodies against GFAP were used to assess astrocyte reactivity in EAE lesions.
- Cytoskeletal proteins from affected CNS areas were analyzed using polyacrylamide gel electrophoresis.
- GFAP levels were quantified relative to the 70-kD neurofilament protein (NF) to determine the GFAP/NF ratio.
Main Results:
- Intense GFAP staining was observed around EAE lesions, particularly in the cerebellum, periventricular areas, and spinal cord.
- The GFAP/NF protein ratio significantly increased in EAE animals, reaching 2.54 by 6 months post-immunization, compared to stable ratios in controls.
- Elevated GFAP levels were confirmed, suggesting substantial gliosis beyond potential neural fiber reduction.
Conclusions:
- Chronic relapsing EAE in SJL/J mice effectively models the gliotic plaque formation seen in MS.
- This model is suitable for investigating the development and characteristics of glial scars in demyelinating diseases.