| First Author | Ojha J | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 2 | Pages | e16550 |
| PubMed ID | 21379584 | Mgi Jnum | J:171056 |
| Mgi Id | MGI:4948384 | Doi | 10.1371/journal.pone.0016550 |
| Citation | Ojha J, et al. (2011) Behavioral defects in chaperone-deficient Alzheimer's disease model mice. PLoS One 6(2):e16550 |
| abstractText | Molecular chaperones protect cells from the deleterious effects of protein misfolding and aggregation. Neurotoxicity of amyloid-beta (Abeta) aggregates and their deposition in senile plaques are hallmarks of Alzheimer's disease (AD). We observed that the overall content of alphaB-crystallin, a small heat shock protein molecular chaperone, decreased in AD model mice in an age-dependent manner. We hypothesized that alphaB-crystallin protects cells against Abeta toxicity. To test this, we crossed alphaB-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, alphaB-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. |
