Academic Journal
M1 muscarinic acetylcholine receptor dysfunction in moderate Alzheimer's disease pathology
| العنوان: | M1 muscarinic acetylcholine receptor dysfunction in moderate Alzheimer's disease pathology |
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| المؤلفون: | Yi, Jee Hyun, Whitcomb, Daniel, Park, Se Jin, Martinez Perez, Celia, Barbati, Saviana, Mitchell, Scott, Cho, Kwangwook |
| المصدر: | Yi , J H , Whitcomb , D , Park , S J , Martinez Perez , C , Barbati , S , Mitchell , S & Cho , K 2020 , ' M1 muscarinic acetylcholine receptor dysfunction in moderate Alzheimer's disease pathology ' , Brain Communications , vol. 2 , no. 2 , fcaa058 . https://doi.org/10.1093/braincomms/fcaa058 |
| سنة النشر: | 2020 |
| المجموعة: | University of Bristol: Bristol Reserach |
| مصطلحات موضوعية: | Alzheimer’s disease, M1 muscarinic acetylcholine receptor (mAChR), metabotropic glutamate receptor 5 (mGluR5), recognition memory |
| الوصف: | Aggregation of amyloid beta and loss of cholinergic innervation in the brain are predominant components of Alzheimer’s disease pathology and likely underlie cognitive impairment. Acetylcholinesterase inhibitors are one of the few treatment options for Alzheimer’s disease, where levels of available acetylcholine are enhanced to counteract the cholinergic loss. However, these inhibitors show limited clinical efficacy. One potential explanation for this is a concomitant dysregulation of cholinergic receptors themselves as a consequence of the amyloid beta pathology. We tested this hypothesis by examining levels of M1 muscarinic acetylcholine receptors in the temporal cortex from seven Alzheimer’s disease and seven non-disease age-matched control brain tissue samples (control: 85 ± 2.63 years old, moderate Alzheimer’s disease: 84 ± 2.32 years old, P-value = 0.721; eight female and six male patients). The samples were categorized into two groups: ‘control’ (Consortium to Establish a Registry for Alzheimer’s Disease diagnosis of ‘No Alzheimer’s disease’, and Braak staging pathology of I–II) and ‘moderate Alzheimer’s disease’ (Consortium to Establish a Registry for Alzheimer’s Disease diagnosis of ‘possible/probable Alzheimer’s disease’, and Braak staging pathology of IV). We find that in comparison to age-matched controls, there is a loss of M1 muscarinic acetylcholine receptors in moderate Alzheimer’s disease tissue (control: 2.17 ± 0.27 arbitrary units, n = 7, Mod-AD: 0.83 ± 0.16 arbitrary units, n = 7, two-tailed t-test, t = 4.248, P = 0.00113). Using a functional rat cortical brain slice model, we find that postsynaptic muscarinic acetylcholine receptor function is dysregulated by aberrant amyloid beta-mediated activation of metabotropic glutamate receptor 5. Crucially, blocking metabotropic glutamate receptor 5 restores muscarinic acetylcholine receptor function and object recognition memory in 5XFAD transgenic mice. This indicates that the amyloid beta-mediated activation of metabotropic glutamate receptor 5 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.1093/braincomms/fcaa058 |
| الاتاحة: | https://hdl.handle.net/1983/0bb82389-6677-45bc-99f1-a840a52b8ad8 https://research-information.bris.ac.uk/en/publications/0bb82389-6677-45bc-99f1-a840a52b8ad8 https://doi.org/10.1093/braincomms/fcaa058 https://research-information.bris.ac.uk/ws/files/246752981/fcaa058.pdf |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.2CA68D01 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/braincomms/fcaa058 |
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