Central Histaminergic Signaling, Neural Excitability and Epilepsy

Abstract

Epilepsy is a common neurological disorder characterized by repeated and spontaneous epileptic seizures, which is not well controlled by current medication. Traditional theory supports that epilepsy results from the imbalance of excitatory glutamate neurons and inhibitory GABAergic neurons. Recently, shreds of evidence from available clinical and preclinical researches suggest that histamine in the central nervous system plays an important role in the modulation of neural excitability and pathogenesis of epilepsy. Many histamine receptor ligands show positive response in animal epilepsy models, among which the H3R antagonist pitolisant even has shown a good anti-epileptic effect in clinical trials. New insights are focusing on the potential action of histamine receptors to control and treat epilepsy. This review summarizes the findings from animal and clinical researches on the role of brain histamine and histamine receptor in epilepsy. Importantly, we further provide perspectives on some possible research directions for future studies.

Effects of Cyclosporine A and Adalimumab on the expression profiles histaminergic system-associated genes and microRNAs regulating these genes in HaCaT cells

“…The histaminergic system comprises genes coding histamine receptors and enzymes involved in the metabolism of histamine. Additionally, the histaminergic system interacts with other neural systems, including the dopaminergic [ 5 ], GABAergic [ 6 ], opioidergic [ 7 ], noradrenergic [ 40 ], and angiotensynergic systems [ 41 ], which was confirmed using the PANTHER database [ 42 ]. The findings of this study also suggested that the inflammatory condition modulates the histaminergic system and that the histaminergic system-associated genes are involved in the pathogenesis of psoriasis.…”

“…Additionally, HRH4, which is coupled with the Gi protein, downregulates the levels of adenosine 3’ 5’-cyclic monophosphate (cAMP). The functions of the histaminergic system are independent of external stimuli irrespective of the receptor type that is activated [ 3 , 6 , 7 ]. Psoriasis is a chronic, multi-factor, inflammatory skin disease with a complex immunopathogenesis.…”