TNF-NF-kappaB signaling mediates excessive somnolence in hemiparkinsonian rats
| Autor: | Fang-Chia Chang, Pei-Lu Yi, Chin-Yu Lu, Chiung-Hsiang Cheng, Yi-Tse Hsiao, Han-Han Chang, Chon-Haw Tsai |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Parkinson's disease Tyrosine 3-Monooxygenase Leupeptins Substantia nigra Enzyme-Linked Immunosorbent Assay Disorders of Excessive Somnolence Cysteine Proteinase Inhibitors Functional Laterality Statistics Nonparametric Rats Sprague-Dawley Behavioral Neuroscience Microscopy Electron Transmission Parkinsonian Disorders Excessive daytime somnolence Internal medicine medicine Animals Enzyme Inhibitors Slow-wave sleep Neurons CD11b Antigen business.industry Tumor Necrosis Factor-alpha Dopaminergic NF-kappa B Electroencephalography medicine.disease Rats Substantia Nigra Disease Models Animal Endocrinology Gene Expression Regulation Proteasome inhibitor Tumor necrosis factor alpha Microglia medicine.symptom business Somnolence medicine.drug Signal Transduction |
| Zdroj: | Behavioural brain research. 208(2) |
| ISSN: | 1872-7549 |
| Popis: | Daytime somnolence is common in patients with Parkinson's disease (PD); however there is a lack of understanding of the cellular mechanisms involved in mediating these effects. It has been hypothesized that microglial activation and the subsequent increase of pro-inflammatory cytokines play an important role in the pathogenesis of PD. Because some cytokines are involved in the regulation of sleep, this study was designed to determine if tumor necrosis factor (TNF) and interleukin-1beta (IL-1beta), mediate daytime somnolence in the proteasome inhibitor (MG-132)-induced hemiparkinsonian rat model. Our results indicated that microglial activation caused the loss of dopaminergic neurons in the substantia nigra, and the expression of TNF-alpha, but not IL-1beta, increased in the midbrain and hypothalamus in MG-132-induced hemiparkinsonian rats. Slow-wave sleep (SWS) increased after the induction of hemiparkinsonism, but rapid eye movement (REM) sleep was not consistently altered. Application of the TNF receptor fragment (TNFRF) blocked hemiparkinsonism-induced SWS alteration, whereas the IL-1 receptor antagonist (IL-1ra) exhibited no effect. Increased nuclear translocation of NF-kappaB in the midbrain, and the blockade of SWS enhancement in MG-132-induced hemiparkinsonian rats by an inhibitor of NF-kappaB activation indicate that the TNF-NF-kappaB cascade is a critical mediator of MG-132 hemiparkinsonian-induced sleep alteration. This observation suggests potential therapeutic interventions to target the excessive daytime somnolence in patients with PD. |
| Databáze: | OpenAIRE |
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