Dr. Hilmar Bading and his research group at Heidelberg University’s Interdisciplinary Center for Neurosciences in Germany, have discovered the mechanism by which activated neurons produce a neuroprotective protein. The results were published in the Journal, Cell Reports.
“We already knew that brain activity promotes neuroprotection. Now, we have discovered a central mechanism for this process and a key molecule produced by the body to develop a neuroprotective shield,” says Bading. The protein identified protects nerve cells against cell death.
The diminished memory function associated with stroke, as well as neurodegenerative disorders like Alzheimer’s disease, is the result of nerve cell death in the brain. Bading and his lab have published earlier research suggesting that activity in brain cells can prevent cell death.
Bading and his colleagues knew that the neuroprotection of activated neurons was associated with the action of the N-methyl-D-aspartate (NMDA) receptor found in the brain. When brains cells are functioning, they release neurotransmitters that bind to the NMDA receptor, which stimulates the import of calcium into the cell.
The calcium is recruited to the cell’s nucleus where it induces transcription of a cluster of neuroprotective genes. While this mechanism was identified by Bading and colleagues a few years ago, he comments, “It was not clear to us how it leads to a protective shield.”
In further study of the NMDA receptors, the researchers found an explanation as to how they are involved in preventing cell death. If the NMDA receptors were not localized at the synapses – the junction between adjacent neurons – they were unable to offer protection to the cells. In this case, the receptors actually contribute to nerve damage and cell death.
According to Bading, “Life and death are only a few thousandths of a millimeter away from one another. Outside the synapse the NMDA receptor is no longer Dr. Jekyll, it becomes Mr. Hyde.” The current research found these extrasynaptic NMDA receptors are inhibited through the activity of the brain, and that activin A is the protein responsible for activating this process.
Activin A is a key player in wound healing processes and the menstruation cycle, but is also produced in the nervous system in response to neuronal activity. The activin A is capable of reducing the number of NMDA receptors not found at the synapses, which allows for the formation of a neuroprotective shield, Bading explains.
A molecule that is involved in neuroprotection and the development of new nerve cells – brain-derived neurotrophic factor (BDNF) – has also been shown to be influenced by Activin A. “Activin A can therefore be regarded as a crucial activator of a common neuroprotective mechanism in the brain,” says Bading.
This study has identified potential new targets for the development of Alzheimer’s drugs, and other neurodegenerative treatments. Bading and researchers showed that the presence of activin A in mice brains was capable of reducing the damage caused by a stroke.
“Our research results also indicate that activin A may possibly be used to treat Alzheimer’s disease or Huntington’s disease. The characteristic degeneration of nerve cells associated with these two diseases seems to be due to an increased activity of toxic extrasynaptic NMDA receptors,” says Prof. Bading. “In everyday terms the new findings mean: An active brain produces activin A thereby protecting itself from neurodegeneration.”
- Activated neurons produce protective protein against neurodegenerative conditions – http://www.sciencedaily.com/releases/2015/08/150824065021.htm
- Lau, D., Bengtson, C., Buchthal, B., and Bading, H. (2015). BDNF Reduces Toxic Extrasynaptic NMDA Receptor Signaling via Synaptic NMDA Receptors and Nuclear-Calcium-Induced Transcription of inhba/Activin A. Cell Reports. 12, 1-14.