Title: Cyp46-mediated cholesterol loss promotes survival in stressed hippocampal neurons
Authors: Martin, Mauricio ×
Trovo, Laura
Perga, Simona
Sadowska, Agniezska
Rasola, Andrea
Chiara, Federica
Dotti, Carlos #
Issue Date: May-2011
Publisher: Elsevier
Series Title: Neurobiology of Aging vol:32 issue:5 pages:933-943
Abstract: Aged neurons constitute an outstanding example of survival robustness, outliving the accumulation of reactive oxygen species (ROS) derived from various physiological activities. Since during aging hippocampal neurons experience a progressive loss of membrane cholesterol and, by virtue of this, a gradual and sustained increase in the activity of the survival receptor tyrosine kinase TrkB, we have tested in this study if cholesterol loss is functionally associated to survival robustness during aging. We show that old neurons that did not undergo the cholesterol drop, upon knockdown of the cholesterol hydroxylating enzyme Cyp46, presented low TrkB activity and increased apoptotic levels. In further agreement, inducing cholesterol loss in young neurons led to the early appearance of TrkB activity. In vivo, Cyp46 knockdown led to the appearance of damaged hippocampal neurons in old mice exposed to exogenous stressful stimuli. Cholesterol loss seems therefore to contribute to neuronal survival in conditions of prominent stress, either acute or chronic. The relevance of this pathway in health and disease is discussed.
ISSN: 0197-4580
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory of Neuronal Differentiation (VIB-KU Leuven Center for Brain & Disease Research)
× corresponding author
# (joint) last author

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