Decreased Orexin Receptor 1 mRNA Expression in the Locus Coeruleus in Both Tau Transgenic rTg4510 and Tau Knockout Mice and Accompanying Ascending Arousal System Tau Invasion in rTg4510
| العنوان: | Decreased Orexin Receptor 1 mRNA Expression in the Locus Coeruleus in Both Tau Transgenic rTg4510 and Tau Knockout Mice and Accompanying Ascending Arousal System Tau Invasion in rTg4510 |
|---|---|
| المؤلفون: | Romke Bron, Daniel Hoyer, Ryan J. Keenan, Cameron J Nowell, Leesa M. Challis, Laura H. Jacobson, Sara Oberrauch |
| المصدر: | Journal of Alzheimer's Disease. 79:693-708 |
| بيانات النشر: | IOS Press, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Lateral hypothalamus, Mice, Transgenic, tau Proteins, In situ hybridization, Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Orexin Receptors, Internal medicine, mental disorders, medicine, Animals, RNA, Messenger, Cognitive decline, In Situ Hybridization, Mice, Knockout, General Neuroscience, General Medicine, medicine.disease, Orexin receptor, Orexin, Mice, Inbred C57BL, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Endocrinology, nervous system, Hypothalamic Area, Lateral, Locus coeruleus, Female, Locus Coeruleus, Wakefulness, Geriatrics and Gerontology, Arousal, 030217 neurology & neurosurgery, Narcolepsy |
| الوصف: | Background: Sleep/wake disturbances (e.g., insomnia and sleep fragmentation) are common in neurodegenerative disorders, especially Alzheimer’s disease (AD) and frontotemporal dementia (FTD). These symptoms are somewhat reminiscent of narcolepsy with cataplexy, caused by the loss of orexin-producing neurons. A bidirectional relationship between sleep disturbance and disease pathology suggests a detrimental cycle that accelerates disease progression and cognitive decline. The accumulation of brain tau fibrils is a core pathology of AD and FTD-tau and clinical evidence supports that tau may impair the orexin system in AD/FTD. This hypothesis was investigated using tau mutant mice. Objective: To characterize orexin receptor mRNA expression in sleep/wake regulatory brain centers and quantify noradrenergic locus coeruleus (LC) and orexinergic lateral hypothalamus (LH) neurons, in tau transgenic rTg4510 and tau–/– mice. Methods: We used i n situ hybridization and immunohistochemistry (IHC) in rTg4510 and tau–/– mice. Results: rTg4510 and tau–/– mice exhibited a similar decrease in orexin receptor 1 (OX1R) mRNA expression in the LC compared with wildtype controls. IHC data indicated this was not due to decreased numbers of LC tyrosine hydroxylase-positive (TH) or orexin neurons and demonstrated that tau invades TH LC and orexinergic LH neurons in rTg4510 mice. In contrast, orexin receptor 2 (OX2R) mRNA levels were unaffected in either model. Conclusion: The LC is strongly implicated in the regulation of sleep/wakefulness and expresses high levels of OX1R. These findings raise interesting questions regarding the effects of altered tau on the orexin system, specifically LC OX1Rs, and emphasize a potential mechanism which may help explain sleep/wake disturbances in AD and FTD. |
| تدمد: | 1875-8908 1387-2877 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a213ddff5314c7e8db45905e9d29fc80Test https://doi.org/10.3233/jad-201177Test |
| رقم الانضمام: | edsair.doi.dedup.....a213ddff5314c7e8db45905e9d29fc80 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18758908 13872877 |
|---|