Neural stem cells are not only responsible for early brain development – they remain active for an entire lifetime. They divide and continually generate new nerve cells and enable the brain to constantly adapt to new demands. Various genetic mutations impede neural stem cell activity and thus lead to learning and memory deficits in the people affected. Very little has hitherto been known about the mechanisms responsible for this.
Enzyme regulates brain stem cell activity
An international research team led by Sebastian Jessberger, professor at the Brain Research Institute at the University of Zurich (UZH), is now demonstrating for the first time that a lipid metabolism enzyme regulates the lifelong activity of brain stem cells, in a study published in Cell Stem Cell. This enzyme – known as fatty acid synthase (FASN) – is responsible for the formation of fatty acids. A specific mutation in the enzyme’s genetic information causes cognitive deficits in affected patients.
Headed by postdoc Megan Bowers and PhD candidates Tong Liang and Daniel Gonzalez-Bohorquez, the researchers studied the genetic change of FASN in the mouse model as well as in human cerebral organoids – organ-like cell cultures of the brain that are formed from human embryonic stem cells. “This approach allows us to analyze the effects of the defective enzyme in the brains of adult mice and during early human brain development in parallel,” explains Jessberger. The research involved altering the genetic information of both the mice and the human organoids experimentally so that the lipid metabolism