| Autor: |
Kai Lou, Shudong Liu, Fengxia Zhang, Wenxiu Sun, Xinhuan Su, Wenkai Bi, Qingqing Yin, Yaxin Qiu, Zhenyuan Zhang, Mengzhe Jing, Shizhan Ma |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Journal of Translational Medicine, Vol 21, Iss 1, Pp 1-16 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1479-5876 |
| DOI: |
10.1186/s12967-023-04511-x |
| Popis: |
Abstract Background Increasing evidence has linked the thyroid dysfunction to the pathogenesis of dementia. Evidence from clinical studies has demonstrated that hypothyroidism is related to an increased risk of dementia. But the association of hyperthyroidism with dementia is largely unknown. Methods We used the adenovirus containing thyrotropin receptor (TSHR) amino acid residues 1-289 (Ad-TSHR289)-induced Graves’ disease (GD) phenotype in Alzheimer’s disease (AD) model mice (APP/PS1 mice) to evaluate the effect of hyperthyroidism on the cognitive function and β-amyloid (Aβ) accumulation. Results GD mice exhibited a stable long-term hyperthyroidism and cognitive deficits. Single Cell RNA-sequencing analysis indicated that microglia function played a critical role in the pathophysiological processes in GD mice. Neuroinflammation and polarization of microglia (M1/M2 phenotype) and activated receptor-interacting serine/threonine protein kinase 3 (RIPK3)/mixed lineage kinase domain–like pseudo-kinase (MLKL)-mediated necroptosis contributed to the pathological process, including Aβ deposition and neuronal loss. RIPK3 inhibitor could inhibit GD-mediated Aβ accumulation and neuronal loss. Conclusions Our findings reveal that GD hyperthyroidism aggravates cognitive deficits in AD mice and induces Aβ deposition and neuronal loss by inducing neuroinflammation and RIPK3/MLKL-mediated necroptosis. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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