Role of Histamine in EAE | OptoDrum Paper

Topics:

Autoimmune Demyelinating Diseases

Experimental Autoimmune Encephalomyelitis

Multiple Sclerosis

Neuroinflammation and Autoimmune CNS Disease

Ocular Inflammation and Immune-Mediated Eye Disease

Publication

The Journal of Immunology (Apr 12, 2021) Conditional Deletions of Hdc Confirm Roles of Histamine in Anaphylaxis and Circadian Activity but Not in Autoimmune Encephalomyelitis

Morin F, Singh N, Mdzomba JB, Dumas A, Patenaude A, Pernet V, Vallières L

DOI: 10.4049/jimmunol.2000719 >>

Experimental autoimmune encephalomyelitis (EAE) is the most widely used animal model for multiple sclerosis (MS), an autoimmune disease where the immune system attacks myelin, which coats neurons in the CNS. Histamine has been thought to play a role in MS, effecting disease progression either positively or negatively, depending on the location of histamine action. In this study, Morin et al created a conditional mouse KO model of Hdc, the enzyme that synthesizes histamine, and induced EAE in these mice. Surprisingly, while some phenotypes in these mice were consistent with the lack of histamine, it had no impact on the development and severity of EAE. One behavioral readout of the disease progression in EAE is the decline of visual acuity, which can be measured with our OptoDrum. Consistent with the other observation, visual acuity declined in EAE Hdc-KO animals in the same way as in EAE Hdc-WT animals.

Histamine is best known for its role in allergies, but it could also be involved in autoimmune diseases such as multiple sclerosis. However, studies using experimental autoimmune encephalomyelitis (EAE), the most widely used animal model for multiple sclerosis, have reported conflicting observations and suggest the implication of a nonclassical source of histamine. In this study, we demonstrate that neutrophils are the main producers of histamine in the spinal cord of EAE mice. To assess the role of histamine by taking into account its different cellular sources, we used CRISPR-Cas9 to generate conditional knockout mice for the histamine-synthesizing enzyme histidine decarboxylase. We found that ubiquitous and cell-specific deletions do not affect the course of EAE. However, neutrophil-specific deletion attenuates hypothermia caused by IgE-mediated anaphylaxis, whereas neuron-specific deletion reduces circadian activity. In summary, this study refutes the role of histamine in EAE, unveils a role for neutrophil-derived histamine in IgE-mediated anaphylaxis, and establishes a new mouse model to re-explore the inflammatory and neurologic roles of histamine.

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Role of Histamine in EAE | OptoDrum Paper

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In their recent paper “Conditional Deletions of Hdc Confirm Roles of Histamine in Anaphylaxis and Circadian Activity but Not in Autoimmune Encephalomyelitis” Françoise Morin et al., from the Neuroscience Unit at the Hospital Center of Quebec, Laval University, show that a lack of histamine, unexpectedly, has no impact on the development and severity of Experimental Autoimmune Encephalomyelitis (EAE), the most common animal model for multiple sclerosis (MS).

In their experiments, Morin et al. created a conditional mouse KO model of Hdc, the enzyme that synthesizes histamine, and induced EAE in these mice. One hallmark of EAE disease progression is the decline of visual acuity, which can be measured as a behavioral readout with our OptoDrum. Consistent with their other observations, visual acuity declined in EAE Hdc-KO animals in the same way as in EAE Hdc-WT animals.

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A further example of EAE research can be found in our “OptoDrum Applications” video series.

Products:

OptoDrum

Applications:

Autoimmune Demyelinating Diseases

Experimental Autoimmune Encephalomyelitis

Multiple Sclerosis

Neuroinflammation and Autoimmune CNS Disease

Ocular Inflammation and Immune-Mediated Eye Disease