Behavioral defects in chaperone-deficient Alzheimer's disease model mice

Juhi Ojha, Rajalakshmi V. Karmegam, J. Gunasingh Masilamoni, Alvin V. Terry, Anil G. Cashikar

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Molecular chaperones protect cells from the deleterious effects of protein misfolding and aggregation. Neurotoxicity of amyloid-beta (Aβ) aggregates and their deposition in senile plaques are hallmarks of Alzheimer's disease (AD). We observed that the overall content of αB-crystallin, a small heat shock protein molecular chaperone, decreased in AD model mice in an age-dependent manner. We hypothesized that αB-crystallin protects cells against Aβ toxicity. To test this, we crossed αB-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, αB-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.

Original languageEnglish (US)
Article numbere16550
JournalPloS one
Volume6
Issue number2
DOIs
StatePublished - Feb 28 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Ojha, J., Karmegam, R. V., Gunasingh Masilamoni, J., Terry, A. V., & Cashikar, A. G. (2011). Behavioral defects in chaperone-deficient Alzheimer's disease model mice. PloS one, 6(2), [e16550]. https://doi.org/10.1371/journal.pone.0016550