Paradoxical Sleep Deprivation Modulates Tyrosine Hydroxylase Expression in the Nigrostriatal Pathway and Attenuates Motor Deficits Induced by Dopaminergic Depletion

Paradoxical Sleep Deprivation Modulates Tyrosine Hydroxylase Expression in the Nigrostriatal Pathway and Attenuates Motor Deficits Induced by Dopaminergic Depletion

Author Lima, Marcelo M. S. Google Scholar
Andersen, Monica Levy Autor UNIFESP Google Scholar
Reksidler, Angela B. Google Scholar
Ferraz, Anete C. Google Scholar
Vital, Maria Aparecida Barbato Frazão Autor UNIFESP Google Scholar
Tufik, Sergio Autor UNIFESP Google Scholar
Institution Univ Fed Parana
Universidade Federal de São Paulo (UNIFESP)
Abstract The nigrostriatal pathway is very likely involved in sleep regulation, considering the occurrence and high prevalence of sleep-related disorders in patients with Parkinson's disease. Indeed, dopaminergic neurons in the ventral tegmental area were recently shown to fire in bursts during paradoxical sleep (PS), but little is known about the activity of the nigrostriatal dopamine (DA) cells in relation to PS. In view of that we hypothesized that paradoxical sleep deprivation (PSD) may play a relevant role in nigrostriatal tyrosine hydroxylase (TH) expression and, subsequently, in sleep rebound. The present study was designed to determine the effects of PSD in the nigrostriatal pathway in mice by means of neurochemical and behavioral approaches. Intraperitoneal reserpine (1 mg/kg) associated to alpha-methyl-p-tyrosine (MT) (250 mg/kg) to produce catecholamine depletion, or rotenone (10 mg/kg) to increase striatal DA turnover were injected 30 min before the 24 h of PSD. Catalepsy and open-field tests indicated that motor deficits induced by reserpine-MT were counteracted by PSD, which, in contrast, potentiated the motor impairment induced by rotenone. Besides, PSD produced down-regulation on TH expression within the substantia nigra pars compacta and striatum, without affecting the number or the optical density of dopaminergic neurons present in the respective areas. Interestingly, PSD potentiated the down-regulation of TH expression in the substantia nigra pars compacta and striatum induced by the co-administration of reserpine-MT. These results reinforce the notion of a strong participation of DA in PS, as a consequence of the modulation of TH protein expression in the nigrostriatal pathway..
Keywords alpha-methyl-p-tyrosine
dopamine
paradoxical sleep deprivation
Parkinson's disease
reserpine
rotenone
Language English
Sponsor AFIP
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 06/55968-6
FAPESP: 98/14.303-3
Date 2012-06-01
Published in Cns & Neurological Disorders-drug Targets. Sharjah: Bentham Science Publ Ltd, v. 11, n. 4, p. 359-368, 2012.
ISSN 1871-5273 (Sherpa/Romeo, impact factor)
Publisher Bentham Science Publ Ltd
Extent 359-368
Origin https://dx.doi.org/10.2174/187152712800792839
Access rights Closed access
Type Article
Web of Science ID WOS:000304818900005
URI http://repositorio.unifesp.br/11600/43395

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