May 4, 2012 § Leave a comment
A report published in the March 2 issue of Cell reveals a finding that may link microRNAs to memory and the learning process in general. Scientists at the John Hopkins University School of Medicine studied genetic material that controls protein formation in the brain and found that certain microRNAs control the actions of brain-derived neurotrophic factor (BDNF), which are linked to brain cell survival, learning, and memory boosting. These findings implicate that the use of a drug meant to enhance this function may prevent the mental illness that results from brain wasting diseases such as Huntington’s, Alzheimer’s, and Parkinson’s disease.
BDNF, a growth-factor protein, is released in the hippocampus during the learning process. This protein increases the activity of other proteins involved in memory formation, but only increases production of less than 4% of the brain cell proteins. Mollie K. Meffert, M.D., Ph.D., associate professor of biological chemistry and neuroscience at John Hopkins was determined to find out how BDNF decides which proteins to stimulate, and what is the role of the regulatory microRNAs – small molecules that block protein blueprint messages from being transferred to proteins by binding to them. Too many of these within a cell will halt protein production. Likewise, a loss of certain microRNAs will cause a higher production of proteins.
The researchers compared microRNA levels in the brain cells treated with BDNF to those left untreated. The former had lower levels of microRNAs, suggesting that BDNF controls the levels of these microRNAs, in turn affecting protein production. The microRNAs that were disappearing in the presence of BDNF were all Let-7 microRNAs.
The team then genetically engineered neurons that would stop decreasing Let-7 microRNAs to see if the loss of Let-7 microRNAs would cause BDNF to increase production of proteins. Treating the neurons with the BDNF no longer resulted in decreased microRNA levels (or increased learning and memory proteins). The researchers also found more than 174 microRNAs that increased due to the BDNF therapy, suggesting it may also increase other microRNAs, possibly decreasing the production of proteins that need to be decreased in learning and memory formation.
To confirm these findings, the researchers observed living brain cells to find out how brain messaging responds to the BDNF. The ones that are never translated into the production of proteins can build up within cells. The researchers observed through microscope a lab dish that contained brain cells that had been denoted with a fluorescent molecule. This labeled the formations with glowing spots. Those cells treated with BDNF cells increased in size and number, indicated by the glowing spots. The researchers learned that BDNF uses the microRNA to deliver messages to the spots, where they can be dispelled from the translating apparatus that renders them into proteins.
Meffert said, “Monitoring these fluorescent complexes gave us a window that we needed to understand how BDNF is able to target the production of only certain proteins that help neurons to grow and make learning possible.” He goes on to say that because the team is now aware of how BDNF increases proteins involved in learning and memory formation, they will be able to explore a possible therapy targeted to improve the mechanism in order to treat patients with mental disorders and neurodegenerative diseases.
“Making Memories: How 1 Protein Does It”. (March 5, 2012). Neuroscience News. March 9, 2012. http://neurosciencenews.com/bdnf-micro-rna-protein-making-memories/.
April 1, 2012 § Leave a comment
Huntington’s disease is an heritable, debilitating, congenital neurological disorder in which nerve cells in certain parts of the brain degenerate. It is caused by a defect on chromosome 4. It deprives patients of both muscle coordination and cognitive ability. It involves a slow and painful death.
Thus far, there is no effective treatment for this ailment. But if researchers can build upon the research published this week in the journal Cell Stem Cell.
on a special type of brain cell created from stem cells, they could help restore the muscle coordination that causes the spasms that are distinctive in the disease.
Su-Chan Zhang, neuroscientist at the University of Wisconsin-Madison, senior author of the study said excitedly, “This is really something unexpected!” In the study, locomotion was restored to mice with a Huntington’s-like condition.
Zhang specializes in building different types of brain cells from human embryonic or induced pluripotent stem cells. In this new study, the team concentrated on what are known as GABA neurons, cells that degrade, causing the disruption of a key neural circuit and loss of motor function in Huntington’s patients. Zhang explains that GABA neurons produce a critical neurotransmitter, a chemical that buttresses the communication system in the brain that synchronizes movement.
The team at the UW-Madison Waisman Center learned how to create large amounts of GABA neurons from human embryonic stem cells. They required them for testing in mice models of the disease. The goal was to see if the cells would safely integrate into the mice brains. The results revealed that the cells not only integrated but they also traveled directly to the target, successfully reestablishing the shattered communication network. This worked to restore motor function.
Zhang and others on the team found these results surprising because GABA neurons only reside in one portion of the brain, the basal ganglia, which takes part in a critical role in voluntary motor coordination. The GABA neurons usually act upon cells in the midbrain through the circuit propelled by the GABA neuron chemical neurotransmitter.
Zhang explains, “This circuitry is essential for motor coordination, and it is what is broken in Huntington patients. The GABA neurons exert their influence at a distance through this circuit. Their cell targets are far away.” Therefore, the effective reestablishment of the circuit by the transplanted cells was very surprising. Zhang said, “Many in the field feel that successful cell transplants would be impossible because it would require rebuilding the circuitry. But what we’ve shown is that the GABA neurons can remake the circuitry and produce the right neurotransmitter.”
Findings from the new study are important because they imply that one day it may be possible to use stem cell therapy to treat Huntington’s disease. Also it implies that the adult brain may be more acquiescent than formerly supposed.
Zhang explains that the adult brain is considered stable by neuroscientists. This means it is not very responsive to therapies that seek to correct for things like broken circuitry at the heart of Huntington’s. Zhang says, “The brain is wired in such a precise way that if a neuron projects the wrong way, it could be chaotic.”
Zhang expresses that moving from the mice model to the adult patient will take time and effort, but the findings still prove groundbreaking for those with Huntington’s, a disease for which there has been heretofore no hope.
“Huntington’s Disease – Huntington Chorea.” (April 30, 2011). PubMed Health. A.D.A.M. Medical Encyclopedia. March 18, 2012. http://www.ncbi.nlm.nih.gov/pubmedhealth/ PMH0001775/.
“Stem Cells Hint at Potential Treatment of Huntington’s Disease”. (March 15, 2012). Neuroscience News. March 18, 2012. http://neurosciencenews.com/stem-cell-treatment-huntingtons-disease-gaba-neurons/.