A new role of cholesterol in the brain
Cholesterol alters the function of receptors which are essential for learning and memory. This discovery was made by scientists from the Department of Cellular Neurophysiology, who study the pharmacology of receptors important for the proper function of human brain.
It has been known for a long time that each cell of the human body contains cholesterol. Cholesterol is an essential component of biological membranes, which form the surface of human cells. Besides other proteins, neuronal surface membrane contains glutamate receptors (NMDA and AMPA), which mediate signal transmission between neurons and play a crucial role in memory formation and storage. However, their impaired function or excessive activation contributes to the pathology of numerous neurodegenerative diseases.
One of the long-term goals of the Department of Cellular neurophysiology is to study glutamate receptor properties. Scientists from this department have recently described a strong dependence of NMDA receptors on cholesterol. NMDA receptors play an essential role in memory formation and their function can be virtually abolished by cholesterol depletion. On the other hand, the function of AMPA receptors, which are important for storing the memory, is completely independent of cholesterol.
The findings of Czech scientists were welcomed by the scientific community. The Journal of Physiology published a special commentary (Perspectives) by Lonnie Wollmuth, a world- renowned expert on glutamate receptors. Wollmuth calls the published results "the first glimpse into the intriguing issue, which will no doubt receive increasing attention of scientists" who study neurodegeneration and schizophrenia.
A) Responses of NMDA receptors are virtually abolished after long-term cholesterol depletion. B) Microscopy shows equal numbers of green-labeled NMDA receptors on the surface of a control neuron and a cholesterol-depleted neuron. This shows that cholesterol depletion does not remove NMDA receptors from the cell surface but they lose their function.
Miloslav Korinek, Vojtech Vyklicky, Jirina Borovska, Katarina Lichnerova, Martina Kaniakova, Barbora Krausova, Jan Krusek, Ales Balik, Tereza Smejkalova, Martin Horak and Ladislav Vyklicky: Cholesterol modulates open probability and desensitization of NMDA receptors, Journal of Physiology 2015, Volume 593, Issue 10, pages 2279–2293