Genetic lack of histamine upregulates dopamine neurotransmission and alters rotational behavior but not levodopa-induced dyskinesia in a mouse model of Parkinson’s disease

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Koski , S K , Leino , S , Panula , P , Rannanpää , S & Salminen , O 2020 , ' Genetic lack of histamine upregulates dopamine neurotransmission and alters rotational behavior but not levodopa-induced dyskinesia in a mouse model of Parkinson’s disease ' , Neuroscience Letters , vol. 729 , 134932 . https://doi.org/10.1016/j.neulet.2020.134932

Title: Genetic lack of histamine upregulates dopamine neurotransmission and alters rotational behavior but not levodopa-induced dyskinesia in a mouse model of Parkinson’s disease
Author: Koski, Sini K.; Leino, Sakari; Panula, Pertti; Rannanpää, Saara; Salminen, Outi
Contributor: University of Helsinki, Regenerative pharmacology group
University of Helsinki, Division of Pharmacology and Pharmacotherapy
University of Helsinki, Helsinki In Vivo Animal Imaging Platform (HAIP)
University of Helsinki, Division of Pharmacology and Pharmacotherapy
University of Helsinki, Regenerative pharmacology group
Date: 2020-06-11
Language: eng
Number of pages: 6
Belongs to series: Neuroscience Letters
ISSN: 0304-3940
URI: http://hdl.handle.net/10138/316228
Abstract: 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.
Subject: 3112 Neurosciences
histamine
dopamine
striatum
Parkinson’s disease
levodopa
dyskinesia
histidine decarboxylase
METHAMPHETAMINE
Dopamine
Parkinson's disease
MECHANISMS
Histidine decarboxylase
Histamine
Striatum
HISTIDINE-DECARBOXYLASE
H-3 RECEPTORS
MICE
Levodopa
BRAIN
MODULATION
Dyskinesia
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