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

Author(s)

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

• Document type: Journal article
• Source: TRANSLATIONAL PSYCHIATRY; v. 7, APR 11 2017.
• Web of Science Citations: 9

Abstract

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)

• FAPESP's process: 15/25275-8 - Optogenetic investigation of hippocampal ripples influence on prefrontal circuits during contextual fear memory formation
• Grantee: Cleiton Lopes Aguiar
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor