Neurodegeneration of Trigeminal Mesencephalic Neurons by the Tooth Loss Triggers the Progression of Alzheimer’s Disease in 3×Tg-AD Model Mice
| Autor: | Atsushi Yamanaka, Haruka Seki, Ashis Dhar, Haruki Iwai, Rachel Pei-Hsuan Wang, Shin-Ei Matsumoto, Yasumasa Ohyagi, Tetsuya Goto, Eriko Kuramoto, Makoto Michikawa, Hiromitsu Hara, Wai K. Leung, Raymond Chuen-Chung Chang |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Amyloid Hippocampus Mice Transgenic tau Proteins Hippocampal formation Biology amyloid-β 03 medical and health sciences Amyloid beta-Protein Precursor Tooth Loss 0302 clinical medicine Alzheimer Disease medicine Tooth loss Animals Cognitive Dysfunction Neurons Amyloid beta-Peptides Microglia behavior locus coeruleus General Neuroscience Neurodegeneration trigeminal nuclei neurodegeneration General Medicine medicine.disease Barnes maze Psychiatry and Mental health Clinical Psychology Disease Models Animal 030104 developmental biology medicine.anatomical_structure Disease Progression Locus coeruleus Geriatrics and Gerontology medicine.symptom Cognition Disorders Neuroscience Alzheimer’s disease 030217 neurology & neurosurgery Research Article |
| Zdroj: | Journal of Alzheimer's Disease |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | Background The mesencephalic trigeminal nucleus (Vmes) is not only anatomically adjacent to the locus coeruleus (LC) but is also tightly associated with the function of the LC. The LC can be the first area in which Alzheimer's disease (AD) develops, although it is unclear how LC neuronal loss occurs. Objective We investigated whether neuronal death in the Vmes can be spread to adjacent LC in female triple transgenic (3×Tg)-AD mice, how amyloid-β (Aβ) is involved in LC neuronal loss, and how this neurodegeneration affects cognitive function. Methods The molars of 3×Tg-AD mice were extracted, and the mice were reared for one week to 4 months. Immunohistochemical analysis, and spatial learning/memory assessment using the Barnes maze were carried out. Results In 4-month-old 3×Tg-AD mice, aggregated cytotoxic Aβ42 was found in granules in Vmes neurons. Neuronal death in the Vmes occurred after tooth extraction, resulting in the release of cytotoxic Aβ42 and an increase in CD86 immunoreactive microglia. Released Aβ42 damaged the LC, in turn inducing a significant reduction in hippocampal neurons in the CA1 and CA3 regions receiving projections from the LC. Based on spatial learning/memory assessment, after the tooth extraction in the 4-month-old 3×Tg-AD mice, increased latency was observed in 5-month-old 3×Tg-AD mice 1 month after tooth extraction, which is similar increase of latency observed in control 8-month-old 3×Tg-AD mice. Measures of cognitive deficits suggested an earlier shift to dementia-like behavior after tooth extraction. Conclusion These findings suggest that tooth extraction in the predementia stage can trigger the spread of neurodegeneration from the Vmes, LC, and hippocampus and accelerate the onset of dementia. |
| Databáze: | OpenAIRE |
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