A Selective Histamine H4 Receptor Antagonist, JNJ7777120, Role on glutamate Transporter Activity in Chronic Depression

Glutamate release and reuptake play a key role in the pathophysiology of depression. glutamatergic nerves in the hippocampus region are modulated by histaminergic afferents. Excessive accumulation of glutamate in the synaptic area causes degeneration of neuron cells. The H4 receptor is defined as th...

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Published in:Journal of personalized medicine 2022-02, Vol.12 (2), p.246
Main Authors: Yeni, Yesim, Cakir, Zeynep, Hacimuftuoglu, Ahmet, Taghizadehghalehjoughi, Ali, Okkay, Ufuk, Genc, Sidika, Yildirim, Serkan, Saglam, Yavuz Selim, Calina, Daniela, Tsatsakis, Aristidis, Docea, Anca Oana
Format: Article
Language:English
Subjects:
Animals
Cell viability
COVID-19
Degeneration
Dehydrogenases
Glutamatergic transmission
Glutamic acid transporter
Histamine
Histamine receptors
Immune system
Inflammation
Mental depression
Mental disorders
Nerves
Neurotoxicity
Pathophysiology
Precision medicine
Sucrose
Voltammetry
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Summary:Glutamate release and reuptake play a key role in the pathophysiology of depression. glutamatergic nerves in the hippocampus region are modulated by histaminergic afferents. Excessive accumulation of glutamate in the synaptic area causes degeneration of neuron cells. The H4 receptor is defined as the main immune system histamine receptor with a pro-inflammatory role. To understand the role of this receptor, the drug JNJ7777120 was used to reveal the chronic depression-glutamate relationship. We have important findings showing that the H4 antagonist increases the glutamate transporters' instantaneous activity. In our experiment, it has been shown that blocking the H4 receptor leads to increased neuron cell viability and improvement in behavioral ability due to glutamate. Therefore, JNJ can be used to prevent neurotoxicity, inhibit membrane phospholipase activation and free radical formation, and minimize membrane disruption. In line with our findings, results have been obtained that indicate that JNJ will contribute to the effective prevention and treatment of depression.
ISSN:2075-4426
2075-4426
DOI:10.3390/jpm12020246