Transcriptional, Behavioral and Biochemical Profiling in the 3xTg-AD Mouse Model Reveals a Specific Signature of Amyloid Deposition and Functional Decline in Alzheimer’s Disease
| Autor: | Navei Cerda-Hernández, Federico Bermúdez-Rattoni, Humberto Gutierrez, Araxi O. Urrutia, Rodrigo Pérez-Ortega, Perla Moreno-Castilla, Mayra L Ruiz-Tejada-Segura, Atahualpa Castillo-Morales, Wencheng Yin, Jimena Monzón-Sandoval |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
memory decline
biology Amyloid beta General Neuroscience Neurodegeneration neurodegeneration medicine.disease Insular cortex lcsh:RC321-571 beta amyloid deposits Transcriptome medicine biology.protein Dementia Alzheimer's disease Cognitive decline Gene Neuroscience lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry transcriptome Alzheimer’s Original Research dementia |
| Zdroj: | Frontiers in Neuroscience Frontiers in Neuroscience, Vol 14 (2020) Yin, W, Cerda Hernandez, N, Castillo Morales, A, Ruiz Tejada Segura, M, Monzón Sandoval, J, Moreno Castillo, P, Perez Ortega, R, Bermudez Rattoni, F, Urrutia, A & Gutierrez, H 2020, ' Transcriptional, behavioural and biochemical profiling in the 3xTg-AD mouse model reveals a specific signature of amyloid deposition and functional decline in Alzheimer’s disease ', Frontiers in Neuroscience, vol. 14, 602642 . https://doi.org/10.3389/fnins.2020.602642 |
| ISSN: | 1662-453X 1662-4548 |
| DOI: | 10.3389/fnins.2020.602642 |
| Popis: | Alzheimer’s disease (AD)-related degenerative decline is associated to the presence of amyloid beta (Aβ) plaque lesions and neuro fibrillary tangles (NFT). However, the precise molecular mechanisms linking Aβ deposition and neurological decline are still unclear. Here we combine genome-wide transcriptional profiling of the insular cortex of 3xTg-AD mice and control littermates from early through to late adulthood (2–14 months of age), with behavioral and biochemical profiling in the same animals to identify transcriptional determinants of functional decline specifically associated to build-up of Aβ deposits. Differential expression analysis revealed differentially expressed genes (DEGs) in the cortex long before observed onset of behavioral symptoms in this model. Using behavioral and biochemical data derived from the same mice and samples, we found that down but not up-regulated DEGs show a stronger average association with learning performance than random background genes in control not seen in AD mice. Conversely, these same genes were found to have a stronger association with Aβ deposition than background genes in AD but not in control mice, thereby identifying these genes as potential intermediaries between abnormal Aβ/NFT deposition and functional decline. Using a complementary approach, gene ontology analysis revealed a highly significant enrichment of learning and memory, associative, memory, and cognitive functions only among down-regulated, but not up-regulated, DEGs. Our results demonstrate wider transcriptional changes triggered by the abnormal deposition of Aβ/NFT occurring well before behavioral decline and identify a distinct set of genes specifically associated to abnormal Aβ protein deposition and cognitive decline. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|