WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience Advertisement
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, October 3, 2007, 27(40):10810-10817; doi:10.1523/JNEUROSCI.3269-07.2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bell, K. F. S.
Right arrow Articles by Cuello, A. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bell, K. F. S.
Right arrow Articles by Cuello, A. C.

 Previous Article  |  Next Article 

Neurobiology of Disease
Paradoxical Upregulation of Glutamatergic Presynaptic Boutons during Mild Cognitive Impairment

Karen F. S. Bell,1 David A. Bennett,4 and A. Claudio Cuello1,2,3

Departments of 1Pharmacology and Therapeutics, 2Anatomy and Cell Biology, and 3Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3G 1Y6, and 4Rush Alzheimer's Disease Center, Armour Academic Center, Chicago, Illinois 60612

Correspondence should be addressed to Dr. A. Claudio Cuello, Room 1210, 3655 Sir William Osler Promenade, Montreal, Quebec, Canada H3G 1Y6. Email: claudio.cuello{at}mcgill.ca

Synaptic integrity is now recognized as a central component of Alzheimer's disease. Surprisingly, however, the structural status of glutamatergic synapses in Alzheimer's disease is unclear, despite the fact that glutamate is the major excitatory transmitter of the CNS and has key roles in excitotoxicity and long-term potentiation. The identification of specific markers of glutamatergic neurons now allows an assessment of the structural involvement of the glutamatergic system across progressive stages of the Alzheimer's pathology, an opportunity not afforded by previously used neurochemical approaches. Glutamatergic presynaptic bouton density and dystrophic neurite abundance were quantified in midfrontal gyrus brain tissue from subjects with no cognitive impairment, mild cognitive impairment, or mild- or severe-stage Alzheimer's disease. Our study demonstrates a striking pathology-dependent pattern of glutamatergic synaptic remodeling with disease progression. Subjects with mild cognitive impairment display a paradoxical elevation in glutamatergic presynaptic bouton density, a situation akin to that observed in the cholinergic system, which then depletes and drops with disease progression. This pattern of synaptic remodeling mirrors our previous findings in transgenic animal models and is of major relevance to current transmitter-based therapeutics.

Key words: Alzheimer's disease; mild cognitive impairment; glutamatergic; presynaptic bouton; dystrophic neurite; MMSE

Received March 21, 2007; revised Aug. 21, 2007; accepted Aug. 24, 2007.

Correspondence should be addressed to Dr. A. Claudio Cuello, Room 1210, 3655 Sir William Osler Promenade, Montreal, Quebec, Canada H3G 1Y6. Email: claudio.cuello{at}mcgill.ca






-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2008 by Society for Neuroscience ONLINE ISSN: 1529-2401
-