Neuronal driven pre-plaque inflammation in a transgenic rat model of Alzheimer's disease
| Autor: | Luisa S.B. Pimentel, Simon Allard, A. Claudio Cuello, Sonia Do Carmo, M. Florencia Iulita, Adriana Ducatenzeiler, Cecilia E. Hanzel, Alexa Pichet-Binette |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Aging Pathology medicine.medical_specialty Amyloid BACE1-AS Hippocampus Plaque Amyloid Inflammation Biology Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Alzheimer Disease medicine Animals CX3CL1 030304 developmental biology Neurons 0303 health sciences Amyloid beta-Peptides Microglia General Neuroscience Brain 3. Good health Disease Models Animal medicine.anatomical_structure Cerebral cortex Astrocytes Female Neurology (clinical) Rats Transgenic Geriatrics and Gerontology medicine.symptom Neuroscience 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Neurobiology of Aging. 35:2249-2262 |
| ISSN: | 0197-4580 |
| DOI: | 10.1016/j.neurobiolaging.2014.03.026 |
| Popis: | Chronic brain inflammation is associated with Alzheimer's disease (AD) and is classically attributed to amyloid plaque deposition. However, whether the amyloid pathology can trigger early inflammatory processes before plaque deposition remains a matter of debate. To address the possibility that a pre-plaque inflammatory process occurs, we investigated the status of neuronal, astrocytic, and microglial markers in pre- and post-amyloid plaque stages in a novel transgenic rat model of an AD-like amyloid pathology (McGill-R-Thy1-APP). In this model, we found a marked upregulation of several classical inflammatory markers such as COX-2, IL-1β, TNF-α, and fractalkine (CX3CL1) in the cerebral cortex and hippocampus. Interestingly, many of these markers were highly expressed in amyloid beta-burdened neurons. Activated astrocytes and microglia were associated with these Aβ-burdened neurons. These findings confirm the occurrence of a proinflammatory process preceding amyloid plaque deposition and suggest that Aβ-burdened neurons play a crucial role in initiating inflammation in AD. |
| Databáze: | OpenAIRE |
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