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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, April 22, 2009, 29(16):5108-5115; doi:10.1523/JNEUROSCI.5887-08.2009

This Article Full Text Full Text (PDF) Supplemental Data 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 Similar articles in this journal 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 Google Scholar Google Scholar Articles by Shi, Q. Articles by Yan, R. Search for Related Content PubMed PubMed Citation Articles by Shi, Q. Articles by Yan, R. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Medline Plus Health Information Seniors' Health

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
The Occurrence of Aging-Dependent Reticulon 3 Immunoreactive Dystrophic Neurites Decreases Cognitive Function

Qi Shi, ^* Xiangyou Hu, ^* Marguerite Prior, and Riqiang Yan

Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195

Correspondence should be addressed to Dr. Riqiang Yan, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195. Email: yanr{at}ccf.org

Reticulon 3 (RTN3) has been shown to mark a distinct and abundant population of dystrophic neurites named RTN3 immunoreactive dystrophic neurites (RIDNs) in patients' brains of Alzheimer disease (AD). Transgenic mice expressing RTN3 (Tg-RTN3) also spontaneously develop RIDNs. To determine whether RIDNs formed in Tg-RTN3 mice would ever naturally occur in the nontransgenic mouse brain, we targeted our examination to elderly mouse brains on the basis that AD is an age-dependent neurodegenerative disease where the decline in cognitive function becomes progressively increased during the course of the disease. Here, we demonstrate that the distribution of RIDNs is abundant, rather than sporadic, in elderly but not young mouse brains. RIDNs in the elderly brain have two distinct populations: abundantly dispersed RIDNs that can only be marked by RTN3, and less abundantly clustered RIDNs that can be marked by multiple proteins including RTN3, ubiquitin, and phosphorylated neurofilament. The abundance of RIDNs in Tg-RTN3 mice at the age of 3 months resembles that of 24-month-old wild type mice, suggesting that this animal model mimics and accelerates the natural occurrence of RIDNs. Importantly, we demonstrate that preformed RIDNs appear to reduce dendritic spine density and synaptic function. Further analysis from mechanistic studies suggests that elevated levels of RTN3 lead to an imbalance in the axonal transport of RTN3, which results in the accumulation of RTN3 in swollen neurites. Collectively, these results suggest that blocking the formation of RIDNs may be a promising strategy to impede cognitive decline in the elderly and in AD patients.

---

Received Dec. 11, 2008; revised March 17, 2009; accepted March 19, 2009.

Correspondence should be addressed to Dr. Riqiang Yan, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195. Email: yanr{at}ccf.org

This article has been cited by other articles:

				Q. Shi, M. Prior, W. He, X. Tang, X. Hu, and R. Yan Reduced Amyloid Deposition in Mice Overexpressing RTN3 Is Adversely Affected by Preformed Dystrophic Neurites J. Neurosci., July 22, 2009; 29(29): 9163 - 9173. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help