QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 21, 2007, 27(12):3057-3063; doi:10.1523/JNEUROSCI.4371-06.2007

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Fan, R. Articles by Van Nostrand, W. E. Search for Related Content PubMed PubMed Citation Articles by Fan, R. Articles by Van Nostrand, W. E.

 Previous Article  |  Next Article 

Neurobiology of Disease
Minocycline Reduces Microglial Activation and Improves Behavioral Deficits in a Transgenic Model of Cerebral Microvascular Amyloid

Rong Fan,¹ Feng Xu,¹ Mary Lou Previti,¹ Judianne Davis,¹ Alicia M. Grande,² John K. Robinson,² and William E. Van Nostrand¹

Departments of ¹Medicine and ²Psychology, Stony Brook University, Stony Brook, New York 11794

Correspondence should be addressed to Dr. William E. Van Nostrand, Department of Medicine, HSC T-15/083, Stony Brook University, Stony Brook, NY 11794-8153. Email: william.vannostrand{at}stonybrook.edu

Cerebral microvascular amyloid ß protein (Aß) 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 Aß 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 Aß 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 Aß or the restriction of fibrillar amyloid to the cerebral microvasculature. Similarly, minocycline-treated Tg-SwDI mice exhibited no change in the levels of total Aß, the ratios of Aß40 and Aß42, or the amounts of soluble, insoluble, or oligomeric Aß 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 Aß.

Key words: cerebral microvascular amyloid; neuroinflammation; cognitive impairment; microglia; transgenic mice; behavior

---

Received Oct. 6, 2006; revised Jan. 29, 2006; accepted Feb. 11, 2007.

Correspondence should be addressed to Dr. William E. Van Nostrand, Department of Medicine, HSC T-15/083, Stony Brook University, Stony Brook, NY 11794-8153. Email: william.vannostrand{at}stonybrook.edu

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2007 27: i. [Full Text]  

This article has been cited by other articles:

				F. Xu, M. P. Vitek, C. A. Colton, M. L. Previti, N. Gharkholonarehe, J. Davis, and W. E. Van Nostrand Human Apolipoprotein E Redistributes Fibrillar Amyloid Deposition in Tg-SwDI Mice J. Neurosci., May 14, 2008; 28(20): 5312 - 5320. [Abstract] [Full Text] [PDF]

				S. S. El-Amouri, H. Zhu, J. Yu, R. Marr, I. M. Verma, and M. S. Kindy Neprilysin: An Enzyme Candidate to Slow the Progression of Alzheimer's Disease Am. J. Pathol., May 1, 2008; 172(5): 1342 - 1354. [Abstract] [Full Text] [PDF]

				A. Bosco, D. M. Inman, M. R. Steele, G. Wu, I. Soto, N. Marsh-Armstrong, W. C. Hubbard, D. J. Calkins, P. J. Horner, and M. L. Vetter Reduced Retina Microglial Activation and Improved Optic Nerve Integrity with Minocycline Treatment in the DBA/2J Mouse Model of Glaucoma Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1437 - 1446. [Abstract] [Full Text] [PDF]

				W. Cao, H.-J. Song, T. Gangi, A. Kelkar, I. Antani, D. Garza, and M. Konsolaki Identification of Novel Genes That Modify Phenotypes Induced by Alzheimer's {beta}-Amyloid Overexpression in Drosophila Genetics, March 1, 2008; 178(3): 1457 - 1471. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help