Unraveling a new circuitry for sleep regulation in Parkinson's disease.
Sleep disturbances are among the most disabling non-motor symptoms in Parkinson's disease. The pedunculopontine tegmental nucleus and basal ganglia are likely involved in these dysfunctions, as they are affected by neurodegeneration in Parkinson's disease and have a role in sleep regulation. To investigate this, we promoted a lesion in the pedunculopontine tegmental nucleus or substantia nigra pars compacta of male rats, followed by 24 h of REM sleep deprivation. Then, we administrated a dopaminergic D2 receptor agonist, antagonist or vehicle directly in the striatum. After a period of 24 h of sleep-wake recording, we observed that the ibotenic acid infusion in the pedunculopontine tegmental nucleus blocked the so-called sleep rebound effect mediated by REM sleep deprivation, which was reversed by striatal D2 receptors activation. Rotenone infusion in the substantia nigra pars compacta also blocked the sleep rebound, however, striatal D2 receptors activation did not reverse it. In addition, rotenone administration decreased the time spent in NREM sleep, which was corroborated by positive correlations between dopamine levels in both substantia nigra pars compacta and striatum and the time spent in NREM sleep. These findings suggest a new circuitry for sleep regulation in Parkinson's disease, involving the triad composed by pedunculopontine nucleus, substantia nigra pars compacta and striatum, evidencing a potential therapeutic target for the sleep disturbances associated to this pathology.
Laboratório de Neurofisiologia, Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, Brazil.
Adriano D S
AD
Targa
Laboratório de Neurofisiologia, Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, Brazil.
Lais S
LS
Rodrigues
Laboratório de Neurofisiologia, Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, Brazil.
Ana Carolina D
AC
Noseda
Laboratório de Neurofisiologia, Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, Brazil.
Mariana F
MF
Aurich
Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
Monica L
ML
Andersen
Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
Sergio
S
Tufik
Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, Brazil.
Cláudio
C
da Cunha
Laboratório de Neurofisiologia, Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, Brazil. Electronic address: marcelomslima.neuro@gmail.com.
Marcelo M S
MM
Lima
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D065842:Pars Compacta / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology*
D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D015102:3,4-Dihydroxyphenylacetic Acid; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol
Dopamine; Parkinson's disease; Pedunculopontine nucleus; Sleep regulation; Striatum; Substantia nigra pars compacta