Histamine-induced plasticity and gene expression in corticostriatal pathway under hyperammonemia
| Autor: | Filipe Rodrigues Almeida, Hans-Jürgen Bidmon, Olga A. Sergeeva, Helmut L. Haas, Dieter Häussinger, A. N. Chepkova, Boris Görg |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male hyperammonemia striatum Gene Expression Striatum Pharmacology Biology Histamine Agonists 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Organ Culture Techniques Dopamine Physiology (medical) Neural Pathways medicine Animals Pharmacology (medical) Receptor Cerebral Cortex Mice Knockout Neuronal Plasticity synaptic plasticity Histaminergic Hyperammonemia Original Articles medicine.disease histamine Corpus Striatum Psychiatry and Mental health 030104 developmental biology chemistry Synaptic plasticity Original Article Histamine H3 receptor 030217 neurology & neurosurgery Histamine medicine.drug Histamine H3 Antagonists |
| Zdroj: | CNS Neuroscience & Therapeutics |
| ISSN: | 1755-5949 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text