Expression of Phenotypic Astrocyte Marker Is Increased in a Transgenic Mouse Model of Alzheimer's Disease versus Age-Matched Controls: A Presymptomatic Stage Study
| Autor: | Cécile Delarasse, Guylène Page, Sylvie Chalon, Aurélie Doméné, Chelsea Cavanagh, Christophe Klein, Sylvie Bodard, Slavica Krantic |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Aging medicine.medical_specialty Pathology Article Subject Cognitive Neuroscience medicine.medical_treatment Hippocampus lcsh:Geriatrics Biology lcsh:RC321-571 Proinflammatory cytokine 03 medical and health sciences Behavioral Neuroscience Cellular and Molecular Neuroscience 0302 clinical medicine Western blot Internal medicine medicine lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry medicine.diagnostic_test Dentate gyrus Blot lcsh:RC952-954.6 030104 developmental biology Cytokine medicine.anatomical_structure Endocrinology Neurology Neurology (clinical) 030217 neurology & neurosurgery Research Article Astrocyte |
| Zdroj: | International Journal of Alzheimer's Disease, Vol 2016 (2016) International Journal of Alzheimer's Disease |
| Popis: | Recent mouse studies of the presymptomatic stage of Alzheimer’s disease (AD) have suggested that proinflammatory changes, such as glial activation and cytokine induction, may occur already at this early stage through unknown mechanisms. Because TNFαcontributes to increased Aβproduction from the Aβprecursor protein (APP), we assessed a putative correlation between APP/Aβand TNFαduring the presymptomatic stage as well as early astrocyte activation in the hippocampus of 3-month-old APPswe/PS1dE9 mice. While Western blots revealed significant APP expression, Aβwas not detectable by Western blot or ELISA attesting that 3-month-old, APPswe/PS1dE9 mice are at a presymptomatic stage of AD-like pathology. Western blots were also used to show increased GFAP expression in transgenic mice that positively correlated with both TNFαand APP, which were also mutually correlated. Subregional immunohistochemical quantification of phenotypic (GFAP) and functional (TSPO) markers of astrocyte activation indicated a selective and significant increase in GFAP-immunoreactive (IR) cells in the dentate gyrus of APPswe/PS1dE9 mice. Our data suggest that subtle morphological and phenotypic alterations, compatible with the engagement of astrocyte along the activation pathway, occur in the hippocampus already at the presymptomatic stage of AD. |
| Databáze: | OpenAIRE |
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