Journal Article

Rescue from excitotoxicity and axonal degeneration accompanied by age-dependent behavioral and neuroanatomical alterations in caspase-6-deficient mice

Valeria Uribe, Bibiana K.Y. Wong, Rona K. Graham, Corey L. Cusack, Niels H. Skotte, Mahmoud A. Pouladi, Yuanyun Xie, Konstantin Feinberg, Yimiao Ou, Yingbin Ouyang, Yu Deng, Sonia Franciosi, Nagat Bissada, Amanda Spreeuw, Weining Zhang, Dagmar E. Ehrnhoefer, Kuljeet Vaid, Freda D. Miller, Mohanish Deshmukh, David Howland and Michael R. Hayden

in Human Molecular Genetics

Volume 21, issue 9, pages 1954-1967
Published in print May 2012 | ISSN: 0964-6906
Published online January 2012 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/dds005
Rescue from excitotoxicity and axonal degeneration accompanied by age-dependent behavioral and neuroanatomical alterations in caspase-6-deficient mice

Show Summary Details

Preview

Apoptosis, or programmed cell death, is a cellular pathway involved in normal cell turnover, developmental tissue remodeling, embryonic development, cellular homeostasis maintenance and chemical-induced cell death. Caspases are a family of intracellular proteases that play a key role in apoptosis. Aberrant activation of caspases has been implicated in human diseases. In particular, numerous findings implicate Caspase-6 (Casp6) in neurodegenerative diseases, including Alzheimer disease (AD) and Huntington disease (HD), highlighting the need for a deeper understanding of Casp6 biology and its role in brain development. The use of targeted caspase-deficient mice has been instrumental for studying the involvement of caspases in apoptosis. The goal of this study was to perform an in-depth neuroanatomical and behavioral characterization of constitutive Casp6-deficient (Casp6−/−) mice in order to understand the physiological function of Casp6 in brain development, structure and function. We demonstrate that Casp6−/− neurons are protected against excitotoxicity, nerve growth factor deprivation and myelin-induced axonal degeneration. Furthermore, Casp6-deficient mice show an age-dependent increase in cortical and striatal volume. In addition, these mice show a hypoactive phenotype and display learning deficits. The age-dependent behavioral and region-specific neuroanatomical changes observed in the Casp6−/− mice suggest that Casp6 deficiency has a more pronounced effect in brain regions that are involved in neurodegenerative diseases, such as the striatum in HD and the cortex in AD.

Journal Article.  8831 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.