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Updated: Feb 27, 2026
Induction and Clinical Scoring of Chronic-Relapsing Experimental Autoimmune Encephalomyelitis
Published on: July 4, 2007
Elevated serum [Met5]-enkephalin levels correlate with improved clinical and behavioral outcomes in experimental
Michael D Ludwig1, Ian S Zagon1, Patricia J McLaughlin1
1Department of Neural & Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA 17033, United States.
Abstract:
Methionine enkephalin ([Met5]-enkephalin, Opioid growth factor (OGF)) is a small neuropeptide with growth-related as well as immunomodulatory properties. OGF is distributed widely throughout the body, is both autocrine and paracrine produced, and has a very short half-life in serum. In addition to its neurotransmitter functions, OGF inhibits cell replication of a wide variety of cells involved in the autoimmune process. In this preclinical study, mice were immunized with myelin oligodendrocytic glycoprotein (MOG35-55) to establish a chronic progressive form of autoimmune encephalomyelitis (EAE), and serum enkephalin levels were assessed throughout the disease as well as in response to OGF therapy in order to determine whether OGF may be a biological marker for EAE and multiple sclerosis. Immunized mice were randomly assigned to groups receiving daily 10mg/kg OGF (n=24) or saline (n=25) beginning at the time of established disease and clinical behavior. Open field activity, rearing, forced swimming, and novel object tests were monitored. Serum levels of peptide were measured prior to immunization, before clinical symptoms were observed, and at the onset and peak period of disease. Spinal cord neuropathology was evaluated 40days after immunization. EAE disease onset occurred on day 9 post immunization when the mean clinical score was 1.5. Peak disease scores for saline-injected EAE mice reached a mean of 5.7 on day 18, whereas mice receiving OGF had a peak clinical score of 2.5. Behavioral tests conducted 5days post-immunization (and before clinical signs of EAE) revealed that EAE mice had reduced serum enkephalin levels related to elevated clinical disease scores. Serum levels of enkephalin collected at peak disease and after 40days correlated with clinical scores. Disease status was associated with activity in the open field, rearing, time associating with a novel object, and pain sensitivity. Clinical signs of EAE correlated with levels of enkephalins such that as behavioral scores increased, serum [Met5]-enkephalin levels decreased. Thus, [Met5]-enkephalin is a novel biomarker that is associated with disease onset and progression, as well as response to therapy in a mouse model of EAE, and may provide new insight into MS.
Insights
Methionine enkephalin, a neuropeptide, shows potential as a biomarker for autoimmune encephalomyelitis (EAE). Lower levels correlate with increased disease severity, suggesting a role in monitoring EAE and multiple sclerosis progression.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Methionine enkephalin (Opioid growth factor, OGF) is a neuropeptide with immunomodulatory functions.
- OGF inhibits the replication of cells involved in autoimmune processes.
- Its role as a biomarker in autoimmune diseases like EAE and MS is not well-established.
Purpose of the Study:
- To investigate methionine enkephalin (OGF) as a potential biomarker for autoimmune encephalomyelitis (EAE).
- To assess serum enkephalin levels in EAE mice during disease progression and in response to OGF therapy.
- To explore the correlation between enkephalin levels, disease severity, and behavioral changes.
Main Methods:
- A preclinical mouse model of chronic progressive EAE was established using myelin oligodendrocytic glycoprotein (MOG35-55) immunization.
- Mice received daily OGF (10mg/kg) or saline treatment starting at disease onset.
- Serum enkephalin levels were measured at various time points; behavioral tests and spinal cord neuropathology were also evaluated.
Main Results:
- EAE onset occurred on day 9, with peak clinical scores reaching 5.7 in saline-treated mice and 2.5 in OGF-treated mice.
- Reduced serum enkephalin levels were observed in EAE mice before clinical signs and correlated with elevated disease scores.
- Serum enkephalin levels at peak disease and 40 days post-immunization correlated with clinical scores, decreasing as behavioral scores increased.
Conclusions:
- [Met5]-enkephalin serves as a novel biomarker associated with the onset, progression, and therapeutic response in a mouse model of EAE.
- Decreased enkephalin levels correlate with increased EAE severity, suggesting its utility in monitoring disease status.
- These findings may offer new insights into the pathogenesis and management of multiple sclerosis.
