論文 - 詳細
| RRC ID | 89435 |
|---|---|
| 著者 | Nakagawa T, Xie JL, Park K, Cao K, Savadkohighodjanaki M, Zhang YJ, Jun H, Ichii A, Lee JY, Soma S, Medhat YK, Saido TC, Igarashi KM. |
| タイトル | Early dopamine disruption in the entorhinal cortex of a knock-in model of Alzheimer's disease. |
| ジャーナル | Nat Neurosci |
| Abstract |
The entorhinal cortex is a critical brain area for memory formation, while also the region exhibiting the earliest histological and functional alterations in Alzheimer's disease (AD). The entorhinal cortex therefore has been long hypothesized as one of the originating brain areas of AD pathophysiology, although circuit mechanisms causing its selective vulnerability remain poorly understood. Here we show that dopamine neurons projecting their axons to the lateral entorhinal cortex (LEC), critical for memory formation in healthy brains, become dysfunctional from the early pathological stage and cause associative memory impairments in amyloid precursor protein knock-in mice. Dopamine dysfunction led to the disruption of associative memory encoding of LEC layer 2/3. Optogenetic reactivation of LEC dopamine fibers rescued associative learning behavior. L-DOPA treatment restored memory encoding of LEC neurons and associative memory of amyloid precursor protein knock-in mice. These results suggest early dysfunction of LEC-projecting dopamine neurons underlie memory impairment in AD from early stages, pointing to a need for clinical investigation of LEC dopamine in patients with AD. |
| 巻・号 | 29(6) |
| ページ | 1386-1396 |
| 公開日 | 2026-6-1 |
| DOI | 10.1038/s41593-026-02260-w |
| PII | 10.1038/s41593-026-02260-w |
| PMID | 42026254 |
| PMC | PMC13246448 |
| MeSH | Alzheimer Disease* / genetics Alzheimer Disease* / metabolism Alzheimer Disease* / pathology Amyloid beta-Protein Precursor / genetics Animals Disease Models, Animal Dopamine* / metabolism Dopaminergic Neurons* / drug effects Dopaminergic Neurons* / metabolism Dopaminergic Neurons* / pathology Dopaminergic Neurons* / physiology Entorhinal Cortex* / drug effects Entorhinal Cortex* / metabolism Entorhinal Cortex* / pathology Gene Knock-In Techniques Humans Levodopa / pharmacology Levodopa / therapeutic use Male Mice Mice, Inbred C57BL Mice, Transgenic |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 247 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 237.4 |
| リソース情報 | |
| 実験動物マウス | RBRC06344 |