The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism

Autor(es)

Masini, D. ; Lopes-Aguiar, C. ; Bonito-Oliva, A. ; Papadia, D. ; Andersson, R. ; Fisahn, A. ; Fisone, G.

• Tipo de documento: Artigo Científico
• Fonte: TRANSLATIONAL PSYCHIATRY; v. 7, APR 11 2017.
• Citações Web of Science: 9

Resumo

Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor impairment and a wide range of nonmotor symptoms, including sleep disorders and cognitive and affective deficits. In this study, we used a mouse model of PD based on 6-hydroxydopamine (6-OHDA) to examine the effect of thioperamide, a histamine H3 receptor antagonist, on circadian activity, recognition memory and anxiety. A partial, bilateral 6-OHDA lesion of the striatum reduces motor activity during the active phase of the 24 h cycle. In addition, the lesion disrupts the endogenous circadian rhythm observed when mice are maintained in constant darkness. Administration of thioperamide to 6-OHDA-lesion mice rescues the normal rest/activity cycle. Moreover, thioperamide counteracts the deficit of novel object recognition produced by 6-OHDA. Our experiments show that this memory impairment is accompanied by disrupted gamma oscillations in the hippocampus, which are also rescued by thioperamide. In contrast, we do not observe any modification of the anxiogenic effect of 6-OHDA in response to administration of thioperamide. Our results indicate that thioperamide may act as a multifunctional drug, able to counteract disruptions of circadian rhythm and cognitive deficits associated with PD. (AU)

• Processo FAPESP: 15/25275-8 - Investigação optogenética da influência de ripples hipocampais sobre circuitos do córtex pré-frontal durante formação de memória de medo contextual
• Beneficiário: Cleiton Lopes Aguiar
• Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado