期刊
JOURNAL OF NEUROSCIENCE
卷 27, 期 12, 页码 3057-3063出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4371-06.2007
关键词
cerebral microvascular amyloid; neuroinflammation; cognitive impairment; microglia; transgenic mice; behavior
资金
- NINDS NIH HHS [NS36645, R01 NS055118, R01 NS036645, NS55118] Funding Source: Medline
Cerebral microvascular amyloid beta protein (A beta) deposition and associated neuroinflammation is increasingly recognized as an important component leading to cognitive impairment in Alzheimer's disease and related cerebral amyloid angiopathy disorders. Transgenic mice expressing the vasculotropic Dutch/Iowa (E693Q/D694N) mutant human A beta precursor protein in brain (Tg-SwDI) accumulate abundant cerebral microvascular fibrillar amyloid deposits and exhibit robust neuroinflammation. In the present study, we investigated the effect of the anti-inflammatory drug minocycline on A beta accumulation, neuroinflammation, and behavioral deficits in Tg-SwDI mice. Twelve-month-old mice were treated with saline or minocycline by intraperitoneal injection every other day for a total of 4 weeks. During the final week of treatment, the mice were tested for impaired learning and memory. Brains were then harvested for biochemical and immunohistochemical analysis. Minocycline treatment did not alter the cerebral deposition of A beta or the restriction of fibrillar amyloid to the cerebral microvasculature. Similarly, minocycline-treated Tg-SwDI mice exhibited no change in the levels of total A beta, the ratios of A beta 40 and A beta 42, or the amounts of soluble, insoluble, or oligomeric A beta compared with the saline-treated control Tg-SwDI mice. In contrast, the numbers of activated microglia and levels of interleukin-6 were significantly reduced in minocycline-treated Tg-SwDI mice compared with saline-treated Tg-SwDI mice. In addition, there was a significant improvement in behavioral performance of the minocycline-treated Tg-SwDI mice. These finding suggest that anti-inflammatory treatment targeted for cerebral microvascular amyloid-induced microglial activation can improve cognitive deficits without altering the accumulation and distribution of A beta.
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