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P3–286: Aging appears to enhance response of primate microglia to the amyloid–β peptide
Author(s) -
Geula Changiz,
Nicholas Alexander,
El Khoury Joseph
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1555
Subject(s) - microglia , stimulation , toxicity , cortex (anatomy) , chemistry , cerebral cortex , endocrinology , immunology , biology , medicine , neuroscience , inflammation
were used. Inflammatory gene expression was assessed by RPA (in vitro) and RT-PCR (in vivo). Microglial migration and A phagocytosis was examined by Bowden chamber assay and FACS, respectively. A deposition and inflammatory molecules were detecetd by standard and confocal ICH. Results: NE stimulation (10 M) abolished amyloid beta (A ) stimulated microglia chemokine and cytokine expression, while the capacity of microglial cells to migrate and to phagocyte fibrillar amyloid beta peptides increased upon NE stimulation in a concentration dependent manner (10 nM-10 M). Similarly, DSP4 induced LC degeneration and NE depletion of APPV7171I transgenic mice resulted in a pronounced increase of mRNA and protein levels of cytokines, glial fibrillary acidic protein, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Confocal immunohistochemistry revelead that iNOS was expressed by microglial cells in APPV717I control mice, while NE depleted APP717I mice showed a robust neuronal expression of iNOS. COX2 was predominantly expressed by IB4 positive microglial cells. NE depleted APPV717I transgenic mice showed more A 1-40 and 1-42 deposits within the hippocampus and frontal cortex compared to APP transgenic mice with an intact NE innervation. Confocal analysis of microglial cells and A revealed that the number of colabelled cells was significantly higher control APPV717I transgenics compared to NE depleted mice, suggesting that NE levels may modulate microglial phagocytosis also in vivo. Conclusions: Taken together this may indicate that LC degeneration and the subsequent decrease of NE concentrations facillitate the inflammatory reaction of microglial cells. At the same time, impaired microglial clearance may significantly contribute to A deposition in AD.