In two separate studies in mice scheduled to appear online this week and in an upcoming issue of the Proceedings of the National Academy of Sciences, UT Southwestern research teams studied the protein Cdk5 and discovered both helpful and detrimental mechanisms it elicits in nerve cells.
Dr. Amelia Eisch, assistant professor of psychiatry at UT Southwestern, and her colleagues uncovered a beneficial mechanism of the helpful “Dr. Jekyll” side of the Cdk5 protein, which is also thought to kill brain cells and contribute to neurodegenerative diseases such as Alzheimer’s. In the current study, Dr. Eisch found that Cdk5, together with its activating partner molecule p35, helps immature nerve cells become fully functional.
In a separate study, Dr. James Bibb, associate professor of psychiatry at UT Southwestern, found yet another harmful action of the Cdk5 protein. It can stunt learning and reduce motor control.
Cdk5 is a kinase, which means its job is to interact with all sorts of other proteins inside cells and modify them through a process called protein phosphorylation. Whether Cdk5 nurtures or devastates depends on the state of its partner and the proteins it modifies.
“Like all of us, Cdk5 can influence others, in this case other proteins,” Dr. Eisch said. “When Cdk5 messes with hooligans, it causes big trouble. When it hangs with the straight-A students, it actually helps other cells reach their full potential.”
Dr. Eisch studied different stages of neurogenesis, or the formation of new nerve cells, in the brains of adult mice and found that the absence of Cdk5 prevents neural stem cells from maturing. She and her group used advanced genetic engineering to create mice in which they could turn off Cdk5 within nerve cells in a specific region of the brain where new neurons are born.
Dr. Eisch found that when Cdk5 is removed from immature nerve stem cells, normal cell division occurs, but the nerve cells never reach maturity. Researchers also removed Cdk5 from neighboring mature nerve cells and discovered that this removal resulted in the production of fewer immature nerve cells.
“The techniques we used have moved us several steps beyond what is usually done in the field,” Dr. Eisch said. “We’re beginning to assemble a dictionary of what regulates neurogenesis. By understanding what’s vital at each stage of development, we hopefully can one day manipulate human nerve cells so that the brain can withstand neurodegenerative diseases such as Alzheimer’s.”
Dr. Bibb studied the “Mr. Hyde” component of Cdk5. Using a different but equally advanced set of genetic approaches, his team studied the effects of turning Cdk5 to the “dark side” by expressing a shortened form of the Cdk5 activating partner called p25. The group found that when paired with p25 in deep brain structures, Cdk5 had destructive effects on motor coordination and learning in the mice.
Neuropsychiatric illnesses such as schizophrenia, attention deficit hyperactivity disorder and drug addiction involve similar brain pathways as the ones studied and implicated in the “Mr. Hyde” aspect of Cdk5, Dr. Bibb said.
Dr. Bibb also used new technology to reach deeper inside the brain and explore regions beyond those typically examined in conjunction with neurodegenerative diseases. His team used a green fluorescent protein to trace Cdk5’s activity in mice, allowing the researchers to examine precisely what was happening in the brain when the Cdk5/p25 pairing was overexpressed.
They found that the overexpression damaged circuitry in the area of the brain that controls movement and reward-based learning. The brain cells lost about half of their connections, or synapses, with other brain cells. This was accompanied by inflammation usually associated with neurodegeneration.
“Once we saw the loss of synapses, we understood why the mice experienced problems with movement and learning,” Dr. Bibb said. “Surprisingly, despite the negative effects of putting Cdk5 with p25 in this part of the brain, the cells didn’t die. Researchers now have the tools to delve deeper into the brain to study disease. Being unable to control movement, or having psychiatric illness, can be as devastating as memory loss.”
Dr. Eisch will next study why immature cells need Cdk5/p35 and why the loss of Cdk5 in neighboring mature nerve cells stopped development.
Dr. Bibb’s work will focus on blocking Cdk5 from causing negative reactions and trying to determine how Cdk5/p25 is created.
Other UT Southwestern researchers involved in Dr. Eisch’s work were Dr. Diane Lagace, instructor of psychiatry; Dr. David Benavides, resident; and Dr. Bibb. Researchers from the European Institute of Oncology in Italy and Rockefeller University in New York also were involved.
Other UT Southwestern researchers involved in Dr. Bibb’s work were Dr. Douglas Meyer, postdoctoral research fellow in psychiatry; Dr. Edmond Richer, former assistant professor of radiology; Dr. Kanehiro Hayashi, postdoctoral researcher in psychiatry; Carly Hale, student research assistant in psychiatry; Dr. Christopher Cowan, assistant professor of psychiatry; and Dr. Peter Antich, professor of radiology. Researchers from the Centers for Disease Control and Prevention, Massachusetts Institute of Technology, Rockefeller University, Yale University School of Medicine and Connecticut Mental Health Center also were involved.
Dr. Janice Kansy, senior research scientist in psychiatry at UT Southwestern, contributed to both papers.
The Canadian Institute of Health Research, the National Institutes of Health and the Cure Alzheimer’s Fund supported Dr. Eisch’s work.
Dr. Bibb’s research was supported in part by the Gulf War Illness Research Program, the National Institute on Drug Abuse and the National Institute of Mental Health.
Dr. Amelia Eisch -- http://www.utsouthwestern.edu/findfac/professional/0,2356,46980,00.html
Dr. James Bibb -- http://www.utsouthwestern.edu/findfac/professional/0,2356,51415,00.html
LaKisha Ladson | Newswise Science News
Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering