Genetic lack of histamine upregulates dopamine neurotransmission and alters rotational behavior but not levodopa-induced dyskinesia in a mouse model of Parkinson’s disease
| Autor: | Pertti Panula, Saara Rannanpää, Sini K. Koski, Outi Salminen, Sakari Leino |
|---|---|
| Přispěvatelé: | Regenerative pharmacology group, Division of Pharmacology and Pharmacotherapy, University of Helsinki, Faculty of Pharmacy, Helsinki In Vivo Animal Imaging Platform (HAIP), Department of Anatomy, Neuroscience Center, Drug Research Program, DAPHNE - Developing Assessment Practices in Higher Education, Teachers' Academy |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Dyskinesia Drug-Induced striatum Dopamine Parkinson's disease H-3 RECEPTORS Histidine decarboxylase Nigrostriatal pathway METHAMPHETAMINE Synaptic Transmission MECHANISMS Levodopa Mice 03 medical and health sciences 0302 clinical medicine Dopamine receptor D2 medicine Animals BRAIN MODULATION Oxidopamine Levodopa-induced dyskinesia Dyskinesia business.industry Dopaminergic Neurons General Neuroscience Dopaminergic 3112 Neurosciences Histaminergic Parkinson Disease histamine Corpus Striatum Up-Regulation Disease Models Animal 030104 developmental biology medicine.anatomical_structure Parkinson’s disease HISTIDINE-DECARBOXYLASE Histamine H3 receptor medicine.symptom business Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuroscience Letters. 729:134932 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2020.134932 |
| Popis: | The brain histaminergic and dopaminergic systems closely interact, and some evidence also suggests significant involvement of histamine in Parkinson’s disease (PD), where dopaminergic neurons degenerate. To further investigate histamine-dopamine interactions, particularly in the context of PD, a genetic lack of histamine and a mouse model of PD and levodopa-induced dyskinesia were here combined. Dopaminergic lesions were induced in histidine decarboxylase knockout and wildtype mice by 6-hydroxydopamine injections into the medial forebrain bundle. Post-lesion motor dysfunction was studied by measuring drug-induced rotational behavior and dyskinesia. Striatal tissue from both lesioned and naïve animals was used to investigate dopaminergic, serotonergic and histaminergic biomarkers. Histamine deficiency increased amphetamine-induced rotation but did not affect levodopa-induced dyskinesia. qPCR measurements revealed increased striatal expression of D1 and D2 receptor, DARPP-32, and H3 receptor mRNA, and synaptosomal release experiments in naïve mice indicated increased dopamine release. A lack of histamine thus causes pre- and postsynaptic upregulation of striatal dopaminergic neurotransmission which may be reflected in post-lesion motor behavior. Disturbances or manipulations of the histaminergic system may thus have significant consequences for dopaminergic neurotransmission and motor behavior in both healthy and disease conditions. The findings also represent new evidence for the complex interplay between dopamine and histamine within the nigrostriatal pathway. |
| Databáze: | OpenAIRE |
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