title: The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism.
abstract: Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor impairment and a wide range of non-motor 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.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Masini
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Lopes-Aguiar
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Bonito-Oliva
authors.affiliation: Neuronal Oscillations Laboratory, Division for Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Papadia
authors.affiliation: Neuronal Oscillations Laboratory, Division for Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Andersson
authors.affiliation: Neuronal Oscillations Laboratory, Division for Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Fisahn
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Fisone
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D065818:Gamma Rhythm / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D054828:Histamine H3 Antagonists / Q000627:therapeutic use*; D008297:Male; D011939:Mental Recall / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D010880:Piperidines / Q000627:therapeutic use*; D021641:Recognition, Psychology / Q000187:drug effects*
chemical_list: D054828:Histamine H3 Antagonists; D010880:Piperidines; C052075:thioperamide