Scientists at Karolinska Institutet in Sweden have identified two molecules that play an important role in the survival and production of nerve cells in the brain, including nerve cells that produce dopamine. The discovery, which is published in the journal Nature Chemical Biology, may be significant in the long term for the treatment of several diseases, such as Parkinson's disease.
The same scientists have previously shown that receptors known as "liver X receptors" or LXR, are necessary for the production of different types of nerve cells, or neurons, in the developing ventral midbrain. One these types, the midbrain dopamine-producing neurons play an important role in a number of diseases, such as Parkinson's disease.
What was not known, however, was which molecules stimulate LXR in the midbrain, such that the production of new nerve cells could be initiated. The scientists have used mass spectrometry and systematic experiments on zebrafish and mice to identify two molecules that bind to LXR and activate it. These two molecules are named cholic acid and 24,25-EC, and are bile acid and a derivate of cholesterol, respectively. The first molecule, cholic acid, influences the production and survival of neurons in what is known as the "red nucleus", which is important for incoming signals from other parts of the brain. The other molecule, 24,25-EC, influences the generation of new dopamine-producing nerve cells, which are important in controlling movement.
One important conclusion of the study is that 24,25-EC can be used to turn stem cells into midbrain dopamine-producing neurons, the cell type that dies in Parkinson's disease. This finding opens the possibility of using cholesterol derivates in future regenerative medicine, since new dopamine-producing cells created in the laboratory could be used for transplantation to patients with Parkinson's disease.
"We are familiar with the idea of cholesterol as a fuel for cells, and we know that it is harmful for humans to consume too much cholesterol", says Ernest Arenas, Professor of Stem Cell Neurobiology at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet, who led the study. "What we have shown now is that cholesterol has several functions, and that it is involved in extremely important decisions for neurons. Derivatives of cholesterol control the production of new neurons in the developing brain. When such a decision has been taken, cholesterol aids in the construction of these new cells, and in their survival. Thus cholesterol is extremely important for the body, and in particular for the development and function of the brain."
'Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis', Spyridon Theofilopoulos, Yuqin Wang, Satish Srinivas Kitambi, Paola Sacchetti, Kyle M Sousa, Karl Bodin, Jayne Kirk, Carmen Saltó, Magnus Gustafsson, Enrique M Toledo, Kersti Karu, Jan-Åke Gustafsson, Knut R Steffensen, Patrik Ernfors, Jan Sjövall, William J Griffiths, and Ernest Arenas, Nature Chemical Biology, Advance Online Publication 23 December 2012, doi: 10.1038/nchembio.1156.
Karolinska Institutet: http://info.ki.se/ki
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Results of largest ever genetics study of a single population could also help refine dates for major events during human evolution Humans are evolving more rapidly than previously thought, according to the largest ever genetics study of a single population.
Latest genetic tests reveal another break in the male line, potentially undermining the legitimacy of the entire House of Plantagenet When scientists revealed last year that an adulterous affair had apparently broken the male line in Richard III’s family tree, they vowed to investigate further.
By 2016, Icelandic genetics company deCODE will have data on half the country's population. Releasing the data will be controversial, but could save lives
A clinical trial has shown that the drug aducanumab slows cognitive decline in people with Alzheimer's and reduces the amount of amyloid plaque in their brain
A leading researcher issues a call for pills that deliver a full course of treatment in one swallow.One of the world’s preëminent biomedical researchers is calling for a concerted effort by scientists to develop pills that would stay in the stomach or gut for weeks or months once swallowed, delivering one or more drugs continuously or over set intervals.
Two genes responsible for building up drug-resistance can easily be shared between a family of bacteria
When malaria parasites infect blood, they manufacture odor molecules that smell sweet to mosquitoes, scientists report. So how do these odors get from the bloodstream to the insects?
Researchers are developing new method of wireless deep brain stimulation.
Zoos belonging to World Association of Zoos and Aquariums filmed allowing shocking mistreatment of elephants, dolphins, lions, bears, penguins and whales
Owners of Highland Wildlife Park hope Victoria, 18, will get chummy with male Arktos during her stay in the Cairngorms