Circadian dysfunction in response to in vivo treatment with the mitochondrial toxin 3-nitropropionic acid
| Autor: | Dawn H. Loh, Takashi Kudo, Yu Tahara, Daniel D. Truong, Elizabeth Hernández-Echeagaray, Christopher S. Colwell |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Patch-Clamp Techniques DD constant dark Circadian clock Respiratory chain Convulsants Mitochondrion Biology S3 lcsh:RC321-571 Mice suprachiasmatic Internal medicine Circadian Clocks medicine Animals HD Huntingon’s disease Circadian rhythm Gene Knock-In Techniques DIC differential interference contrast lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry PD Parkinson’s disease LD light-dark SCN suprachiasmatic nucleus SFR spontaneous firing rate Suprachiasmatic nucleus 3-NP 3-nitropropionic acid General Neuroscience Period Circadian Proteins i.p. intraperitoneally Nitro Compounds Pathophysiology Mitochondria PER2 Mice Inbred C57BL clock Endocrinology Huntington Disease circadian CT circadian time ZT Zeitgeber time Suprachiasmatic Nucleus Neurology (clinical) Propionates Sleep ACSF artificial CSF (cerebrospinal fluid) Research Article |
| Zdroj: | ASN NEURO ASN Neuro, Vol 6 (2013) |
| ISSN: | 1759-0914 |
| Popis: | Sleep disorders are common in neurodegenerative diseases including Huntington's disease (HD) and develop early in the disease process. Mitochondrial alterations are believed to play a critical role in the pathophysiology of neurodegenerative diseases. In the present study, we evaluated the circadian system of mice after inhibiting mitochondrial complex II of the respiratory chain with the toxin 3-nitropropionic acid (3-NP). We found that a subset of mice treated with low doses of 3-NP exhibited severe circadian deficit in behavior. The temporal patterning of sleep behavior is also disrupted in some mice with evidence of difficulty in the initiation of sleep behavior. Using the open field test during the normal sleep phase, we found that the 3-NP-treated mice were hyperactive. The molecular clockwork responsible for the generation of circadian rhythms as measured by PER2::LUCIFERASE was disrupted in a subset of mice. Within the SCN, the 3-NP treatment resulted in a reduction in daytime firing rate in the subset of mice which had a behavioral deficit. Anatomically, we confirmed that all of the treated mice showed evidence for cell loss within the striatum but we did not see evidence for gross SCN pathology. Together, the data demonstrates that chronic treatment with low doses of the mitochondrial toxin 3-NP produced circadian deficits in a subset of treated mice. This work does raise the possibility that the neural damage produced by mitochondrial dysfunction can contribute to the sleep/circadian dysfunction seen so commonly in neurodegenerative diseases. |
| Databáze: | OpenAIRE |
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