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

卷:729

Article

Koski, Sini K.¹  Leino, Sakari¹  Panula, Pertti^2,3  Rannanpaa, Saara¹  Salminen, Outi¹ 

[1] Univ Helsinki, Fac Pharm, Div Pharmacol & Pharmacotherapy, Helsinki, Finland

[2] Univ Helsinki, Dept Anat, Helsinki, Finland

[3] Univ Helsinki, Neurosci Ctr, Helsinki, Finland

关键词: Histamine;    Dopamine;    Striatum;    Parkinson's disease;    Levodopa;    Dyskinesia;    Histidine decarboxylase;   

DOI  :  10.1016/j.neulet.2020.134932

来源: Elsevier

【 摘 要 】

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 naive 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 naive 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.

【 授权许可】

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