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Dual role of histamine on microglia-induced neurodegeneration
S Barata-Antunes1, A C Cristóvão1, J Pires1
1Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal.
Abstract:
Several hypotheses have been raised about the dual role of histamine in neurological disorders, and evidences have shown its crucial involvement in the modulation of microglia-mediated neuroinflammation. Previously, we reported that the administration of histamine induces a deleterious effect by promoting a pro-inflammatory phenotype on microglia that in turn compromises dopaminergic neuronal survival. Contrary, under lipopolysaccharide challenge, histamine inhibits the injurious effect of microglia-mediated inflammation, protecting dopaminergic neurons, suggesting that the modulation of microglial activity is dependent on the environmental context. Thus, histamine and/or histamine receptor agonists may serve to develop new therapeutic approaches to overcome neurodegenerative disorders.
Insights
Histamine plays a dual role in neurological disorders, influencing microglia-mediated neuroinflammation. Its effects on protecting dopaminergic neurons depend on the specific environmental context, suggesting therapeutic potential.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Histamine's role in neurological disorders is complex, with evidence linking it to microglia-mediated neuroinflammation.
- Previous research indicated histamine administration promotes a pro-inflammatory microglial phenotype, harming dopaminergic neurons.
- The microglial response to histamine appears context-dependent, influencing neuroinflammation and neuronal survival.
Purpose of the Study:
- To investigate the dual role of histamine in modulating microglia-mediated neuroinflammation.
- To explore the impact of histamine on dopaminergic neuronal survival in different inflammatory contexts.
- To assess the therapeutic potential of histamine and its receptor agonists for neurodegenerative disorders.
Main Methods:
- Administration of histamine in a neurological disorder model.
- Lipopolysaccharide (LPS) challenge to induce inflammation.
- Assessment of microglial phenotype and dopaminergic neuronal survival.
Main Results:
- Histamine administration induced a pro-inflammatory microglial phenotype, leading to dopaminergic neuron damage.
- Under LPS challenge, histamine inhibited microglia-mediated inflammation, protecting dopaminergic neurons.
- Microglial response to histamine is modulated by the surrounding environmental context.
Conclusions:
- Histamine exhibits a context-dependent dual role in neuroinflammation and neuroprotection.
- Histamine's modulation of microglial activity is critical in neurological disorders.
- Histamine and histamine receptor agonists represent potential therapeutic strategies for neurodegenerative diseases.
