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Histamine-induced plasticity and gene expression in corticostriatal pathway under hyperammonemia.

ABSTRACT: AIMS:Histamine H3 receptor (H3R) antagonists/inverse agonists increase vigilance. We studied brain histaminergic pathways under hyperammonemia and the transcriptome of receptors and their signaling cascades to provide a rationale for wake-promoting therapies. METHODS:We analyzed histamine-induced long-lasting depression of corticostriatal synaptic transmission (LLDhist). As the expression of dopamine 1 receptors (D1R) is upregulated in LGS-KO striatum where D1R-H3R dimers may exist, we investigated actions of H3R and D1R agonists and antagonists. We analyzed transcription of selected genes in cortex and dorsal striatum in a mouse model of inborn hyperammonemia (liver-specific glutamine synthetase knockout: LGS-KO) and compared it with human hepatic encephalopathy. RESULTS:LGS-KO mice showed significant reduction of the direct depression (DD) but not the long-lasting depression (LLD) by histamine. Neither pharmacological activation nor inhibition of D1R significantly affected DDhist and LLDhist in WT striatum, while in LGS-KO mice D1R activation suppressed LLDhist. Histaminergic signaling was found unchanged at the transcriptional level except for the H2R. A study of cAMP-regulated genes indicated a significant reduction in the molecular signature of wakefulness in the diseased cortex. CONCLUSIONS:Our findings provide a rationale for the development of aminergic wake-promoting therapeutics in hyperammonemic disorders.

SUBMITTER: Sergeeva OA

PROVIDER: S-EPMC7052803 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Histamine-induced plasticity and gene expression in corticostriatal pathway under hyperammonemia.

Sergeeva Olga A OA Chepkova Aisa N AN Görg Boris B Rodrigues Almeida Filipe F Bidmon Hans-Jürgen HJ Haas Helmut L HL Häussinger Dieter D

CNS neuroscience & therapeutics 20190930 3

<h4>Aims</h4>Histamine H3 receptor (H3R) antagonists/inverse agonists increase vigilance. We studied brain histaminergic pathways under hyperammonemia and the transcriptome of receptors and their signaling cascades to provide a rationale for wake-promoting therapies.<h4>Methods</h4>We analyzed histamine-induced long-lasting depression of corticostriatal synaptic transmission (LLDhist). As the expression of dopamine 1 receptors (D1R) is upregulated in LGS-KO striatum where D1R-H3R dimers may exis ...[more]

PMID: 31571389

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Dataset Information

Histamine-induced plasticity and gene expression in corticostriatal pathway under hyperammonemia.

Publications

Histamine-induced plasticity and gene expression in corticostriatal pathway under hyperammonemia.

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