Rescue from excitotoxicity and axonal degeneration accompanied by age-dependent behavioral and neuroanatomical alterations in caspase-6-deficient mice
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Human Molecular Genetics |
Volume | 21 |
Issue number | 9 |
Pages (from-to) | 1954-67 |
Number of pages | 14 |
ISSN | 0964-6906 |
DOIs | |
Publication status | Published - 1 May 2012 |
Externally published | Yes |
- Aging, Alzheimer Disease, Animals, Apoptosis, Base Sequence, Behavior, Animal, Brain, Caspase 6, Humans, Huntington Disease, Mice, Mice, Knockout, Motor Activity, Nerve Degeneration, Neurons, RNA, Messenger, Receptors, N-Methyl-D-Aspartate
Research areas
ID: 153451495