Hdl Handle:
http://hdl.handle.net/10675.2/637
Title:
Behavioral Defects in Chaperone-Deficient Alzheimer's Disease Model Mice
Authors:
Ojha, Juhi; Karmegam, Rajalakshmi V.; Masilamoni, J. Gunasingh; Terry, Alvin V.; Cashikar, Anil G.
Abstract:
Molecular chaperones protect cells from the deleterious effects of protein misfolding and aggregation. Neurotoxicity of amyloid-beta (Ab) aggregates and their deposition in senile plaques are hallmarks of Alzheimer's disease (AD). We observed that the overall content of aB-crystallin, a small heat shock protein molecular chaperone, decreased in AD model mice in an age-dependent manner. We hypothesized that aB-crystallin protects cells against Ab toxicity. To test this, we crossed aB-crystallin/HspB2 deficient (CRYAB-/-HSPB2-/-) mice with AD model transgenic mice expressing mutant human amyloid precursor protein. Transgenic and non-transgenic mice in chaperone-sufficient or deficient backgrounds were examined for representative behavioral paradigms for locomotion and memory network functions: (i) spatial orientation and locomotion was monitored by open field test; (ii) sequential organization and associative learning was monitored by fear conditioning; and (iii) evoked behavioral response was tested by hot plate method. Interestingly, aB-crystallin/HspB2 deficient transgenic mice were severely impaired in locomotion compared to each genetic model separately. Our results highlight a synergistic effect of combining chaperone deficiency in a transgenic mouse model for AD underscoring an important role for chaperones in protein misfolding diseases.
Citation:
PLoS One. 2011 Feb 17; 6(2):e16550
Issue Date:
17-Feb-2011
URI:
http://hdl.handle.net/10675.2/637
DOI:
10.1371/journal.pone.0016550
PubMed ID:
21379584
PubMed Central ID:
PMC3040748
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Center for Molecular Chaperone/Radiobiology & Cancer Virology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorOjha, Juhien_US
dc.contributor.authorKarmegam, Rajalakshmi V.en_US
dc.contributor.authorMasilamoni, J. Gunasinghen_US
dc.contributor.authorTerry, Alvin V.en_US
dc.contributor.authorCashikar, Anil G.en_US
dc.date.accessioned2012-10-26T16:26:57Z-
dc.date.available2012-10-26T16:26:57Z-
dc.date.issued2011-02-17en_US
dc.identifier.citationPLoS One. 2011 Feb 17; 6(2):e16550en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid21379584en_US
dc.identifier.doi10.1371/journal.pone.0016550en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/637-
dc.description.abstractMolecular chaperones protect cells from the deleterious effects of protein misfolding and aggregation. Neurotoxicity of amyloid-beta (Ab) aggregates and their deposition in senile plaques are hallmarks of Alzheimer's disease (AD). We observed that the overall content of aB-crystallin, a small heat shock protein molecular chaperone, decreased in AD model mice in an age-dependent manner. We hypothesized that aB-crystallin protects cells against Ab toxicity. To test this, we crossed aB-crystallin/HspB2 deficient (CRYAB-/-HSPB2-/-) mice with AD model transgenic mice expressing mutant human amyloid precursor protein. Transgenic and non-transgenic mice in chaperone-sufficient or deficient backgrounds were examined for representative behavioral paradigms for locomotion and memory network functions: (i) spatial orientation and locomotion was monitored by open field test; (ii) sequential organization and associative learning was monitored by fear conditioning; and (iii) evoked behavioral response was tested by hot plate method. Interestingly, aB-crystallin/HspB2 deficient transgenic mice were severely impaired in locomotion compared to each genetic model separately. Our results highlight a synergistic effect of combining chaperone deficiency in a transgenic mouse model for AD underscoring an important role for chaperones in protein misfolding diseases.en_US
dc.rightsOjha et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectBiochemistryen_US
dc.subjectProteinsen_US
dc.subjectChaperone Proteinsen_US
dc.subjectBiophysicsen_US
dc.subjectProtein Foldingen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMouseen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectCellular Stress Responsesen_US
dc.subjectNeuroscienceen_US
dc.subjectLearning and Memoryen_US
dc.subjectNeurobiology of Disease and Regenerationen_US
dc.subjectMedicineen_US
dc.subjectClinical Research Designen_US
dc.subjectAnimal Models of Diseaseen_US
dc.subjectNeurologyen_US
dc.subjectDementiaen_US
dc.subjectAlzheimer Diseaseen_US
dc.titleBehavioral Defects in Chaperone-Deficient Alzheimer's Disease Model Miceen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3040748en_US
dc.contributor.corporatenameCenter for Molecular Chaperone/Radiobiology & Cancer Virology-
dc.contributor.corporatenameDepartment of Pharmacology and Toxicology-

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