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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 29, 2009, 29(30):9458-9470; doi:10.1523/JNEUROSCI.2047-09.2009

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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chakroborty, S. Articles by Stutzmann, G. E. PubMed PubMed Citation Articles by Chakroborty, S. Articles by Stutzmann, G. E. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL

 Previous Article  |  Next Article 

Neurobiology of Disease
Deviant Ryanodine Receptor-Mediated Calcium Release Resets Synaptic Homeostasis in Presymptomatic 3xTg-AD Mice

Shreaya Chakroborty, Ivan Goussakov, Megan B. Miller, and Grace E. Stutzmann

Department of Neuroscience, Rosalind Franklin University/The Chicago Medical School, North Chicago, Illinois 60064

Correspondence should be addressed to Dr. Grace E. Stutzmann, Department of Neuroscience, Rosalind Franklin University/The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064. Email: grace.stutzmann{at}rosalindfranklin.edu

Presenilin mutations result in exaggerated endoplasmic reticulum (ER) calcium release in cellular and animal models of Alzheimer's disease (AD). In this study, we examined whether dysregulated ER calcium release in young 3xTg-AD neurons alters synaptic transmission and plasticity mechanisms before the onset of histopathology and cognitive deficits. Using electrophysiological recordings and two-photon calcium imaging in young (6–8 weeks old) 3xTg-AD and non-transgenic (NonTg) hippocampal slices, we show a marked increase in ryanodine receptor (RyR)-evoked calcium release within synapse-dense regions of CA1 pyramidal neurons. In addition, we uncovered a deviant contribution of presynaptic and postsynaptic ryanodine receptor-sensitive calcium stores to synaptic transmission and plasticity in 3xTg-AD mice that is not present in NonTg mice. As a possible underlying mechanism, the RyR2 isoform was found to be selectively increased more than fivefold in the hippocampus of 3xTg-AD mice relative to the NonTg controls. These novel findings demonstrate that 3xTg-AD CA1 neurons at presymptomatic ages operate under an aberrant, yet seemingly functional, calcium signaling and synaptic transmission system long before AD histopathology onset. These early signaling alterations may underlie the later synaptic breakdown and cognitive deficits characteristic of later stage AD.

---

Received April 30, 2009; revised June 2, 2009; accepted June 9, 2009.

Correspondence should be addressed to Dr. Grace E. Stutzmann, Department of Neuroscience, Rosalind Franklin University/The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064. Email: grace.stutzmann{at}rosalindfranklin.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help