Adult Neurogenesis Linked to Lipid Synthesis

Scientists led by Prof Sebastian Jessberger of the University of Zurich’s Brain Research Institute, Switzerland, have discovered that neural stem cells in the adult brain boost their levels of lipid metabolism to grow and generate new neurons.

This image shows stem cells with and without extensions, and the adult nerve cell, shown in red. According to the new study, the key for growth and development of the dividing cell to the adult nerve cell is a massive increase of fatty acid synthesis (Simon Braun / HiFo / UZH)

Neural stem cells generate new neurons every day in two regions of our brain – the hippocampus and the subventricular zone. This process, called adult neurogenesis, is critical for a number of processes implicated in certain forms of learning and memory.

The new study, published in the journal Nature, describes a novel mechanism that plays a key role in adult neurogenesis and is required for the life-long activity of neural stem cells.

“These findings will hopefully give us a new target to develop novel drugs against depression or neurodegenerative diseases,” Prof Jessberger said.

The results show that stem cells depend on glucose-derived production of new fatty acids and lipids. When the key enzyme of this pathway, fatty acid synthase (Fasn), is blocked in neural stem cells, they loose their ability to divide which results in a reduction in newborn neurons.

“To prevent the constant division of neural stem cells, this pathway is regulated by a protein called Spot14, which inhibits lipid synthesis. Controlling Fasn activity is important to make sure that stem cells do not divide too often, which could lead to a premature exhaustion or depletion of the stem cell pool.”

“Surprisingly, the metabolic state of neural stem cells seems to be fundamentally distinct from their daughter cells – newborn neurons – and other dividing cells in the central nervous system. These other cell types are able to take up lipids from the blood stream and use them as important structural components of cell membranes but also for signaling events and as an energy source.”

“Currently, we have to understand in much greater detail why neural stem cells are in this distinct metabolic state; to this end, we are currently performing experiments in the lab with the aim to enhance neurogenesis through manipulation of lipid metabolism,” said Dr Marlen Knobloch of the Brain Research Institute, lead author of the study.

“However, one must not place too high expectations for the quick development of novel drugs. The hope certainly is to increase the number of newborn neurons by targeting lipid metabolism in the human brain,” added study co-author Dr Simon Braun.

This study opens novel therapeutic avenues to treat age- or disease-associated loss of brain cells.

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Bibliographic information: Knobloch M et al. 2012. Metabolic control of adult neural stem cell activity by Fasn-dependent lipogensis. Nature, published online December 02, 2012; doi: 10.1038/nature11689