AI Article Synopsis
- Older brain cells survive better even with damage caused by natural processes like aging.
- Decreasing cholesterol in these brain cells seems to help them stay alive by boosting a survival signal called TrkB.
- Experiments show that young brain cells can gain this survival signal too when they lose cholesterol, which suggests that managing cholesterol might help protect brain cells from stress.
Article 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.
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| http://dx.doi.org/10.1016/j.neurobiolaging.2009.04.022 | DOI Listing |
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