By: CWRU the daily | Published: November 25, 2019
Findings may lead to clues for possible treatments for autism spectrum disorders and schizophrenia
Researchers at the Case Western Reserve University School of Medicine have identified that a gene critical to clearing up unnecessary proteins plays a role in brain development and contributes to the development of autism spectrum disorders (ASD) and schizophrenia.
The discovery, published Nov. 25 in Neuron, provides important insight into the mechanism of both diseases—a possible step toward finding how to treat the disorders.
Cullin 3 is a core component of an E3 ubiquitin ligase responsible for the cell’s clearance of proteins. Mutations of its gene CUL3 have been associated with autism and schizophrenia. However, pathologic mechanisms of CUL3 deficiency have been unclear.
“CUL3 is abundant in the brain, yet little is known of its function,” said Lin Mei, the Allen C. Holmes Professor of Neurological Diseases and chair of the Department of Neurosciences at the Case Western Reserve University School of Medicine. “Here, we show that CUL3 is critical for brain development and communication between cells in the brain.”
Mei, also director of the Cleveland Brain Health Initiative, is the principal investigator with research assistants Zhaoqi Dong and Wenbing Chen. (The published research is titled “CUL3 deficiency causes social deficits and anxiety-like behaviors by impairing excitation-inhibition balance through the promotion of Cap-dependent translation.”)
ASD is a complicated condition that includes difficulty with communication and social interaction, obsessive interests and repetitive behaviors. It affects 1 in 59 children in the United States, according to a recent report by the Centers for Disease Control. Schizophrenia affects about 1 in 100 people worldwide. However, autism and schizophrenia remain among the most mysterious disorders.
Mei and his team studied how CUL3 mutation impacts the brain in mouse models. The researchers were able to demonstrate that altering the gene in mouse models can cause similar social problems that appear in people with these disorders.
Normal mice would spend more time with a mouse over an inanimate object, Mei said. But CUL3-mutant mice couldn’t differentiate between a mouse and an inanimate object, showing a problem with social preference.
In another test, normal mice would spend more time with an unfamiliar mouse over a familiar one. But CUL3-mutant mice couldn’t remember seeing a familiar mouse, suggesting a problem of social memory. Also, CUL3-mutant mice were more anxious than normal mice.
Researchers at Beijing Normal University and the Louis Stokes Cleveland Veterans Affairs Medical Center contributed to the research.
Congratulations! Department of Neurosciences Softball Team are the intramural champions!
Congratulations to Polyxeni Philippidou for her new NIH R01 Award
By: CWRU the daily | Published: September 3, 2019
Neurosciences’ Heather Broihier earns National Institutes of Health honor for outstanding mentorship
Heather Broihier already felt indebted to legendary neurobiologist Story Landis for her scientific success.
After all, Landis founded Case Western Reserve University’s Department of Neurosciences, Broihier’s professional home since 2005. Landis also recruited Lynn Landmesser, the chair who hired Broihier—even though she lacked formal training in neurosciences.
Now Broihier has yet another reason for gratitude—she just won a major National Institutes of Health (NIH) honor for outstanding mentorship. Its name? The Landis Award.
According to current neurosciences department chair Lin Mei, no one deserves the honor more than Broihier. It’s not just that her doctoral students land prestigious positions at places like Vanderbilt and Johns Hopkins universities. Or that she makes sure they have the chance to co-author publications in the field’s leading journals. It’s that she recognizes all of the skills and knowledge necessary for her students to thrive as scientists—and helps them understand the importance of every one.
“She shows them how to do science: the importance of trusting the results of their own experiments and of not worrying too much about what someone else has thought before and what the textbook states,” Mei wrote in Broihier’s nomination letter, adding that her guidance extends well beyond making them technically proficient. “[Each becomes] a critical thinker, public speaker, and writer.”
Broihier sees her efforts as extending the impact of the people whose mentoring made a monumental difference to her, among them Ruth Lehmann, her doctoral adviser at the Massachusetts Institute of Technology, Jim Skeath, her postdoctoral adviser at Washington University, and Landmesser, the chair who took a chance on a researcher with training in biology and genetics seeking a faculty position in neurosciences. In coming to Case Western Reserve, however, Broihier not only found a near-perfect place to pursue developmental neurobiology, but also one with its own strong tradition of mentoring.
“Great mentors make all the difference,” Broihier wrote in the mentorship statement required for Landis consideration. “I know because I have had them.”
A postdoctoral fellow at Stanford University since January, Colleen N. McLaughlin’s time with Brohier included five publications in prominent academic journals and two platform presentations at national conferences en route to earning her PhD last year. But such data points cannot begin to capture Broihier’s influence as a mentor.
“I admire her unique ability to tailor her training to meet the needs of each of her students,” McLaughin explained. “She absolutely deserves this award, and I am incredibly thankful that I had the opportunity to work with her.”
After founding the neurosciences department at Case Western Reserve, Landis went to the the NIH in 1995 to become scientific director for the National Institute of Neurological Disorders and Stroke (NINDS). In 2003, she became the institute’s director, and soon after became a founding co-chair of the NIH Blueprint for Neuroscience Research, whose goal was and is to encourage brain sciences activities that cross multiple NIH institutes. She later played a key role in the 2014 launch of the federal BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, which through 2018 has invested more than $950 million to hundreds of researchers nationwide.
NIH Director Francis Collins described Landis as a “superstar,” one of the agency’s “true giants,” and a “towering intellect” in his letter announcing her retirement five years ago. But when it came time to designate an award in her honor, mentoring was an obvious choice. “An extraordinary individual mentor,” the agency explained in announcing the award last year. “Dr. Landis generously provided her time and energy to support countless scientific investigators…”
The Landis Award is given annually to up to five researchers. It includes a $100,000 supplement to an existing NINDS award, which Broihier will use to support her trainees and perhaps add to their number.
New Undergraduate Neuroscience Courses, Fall 2019
NEUR 301/401 Biological Mechanisms of Brain Disorders (3 credits, MWF, 10:35 - 11:25)
This course will introduce students to a broad range of neurological and neuropsychiatric diseases & disorders in order to understand how genetic and environmental perturbations can disrupt normal brain function. We will address underlying biological mechanisms as well as critical knowledge gaps and current efforts to develop treatments.
Taught by faculty from the School of Medicine (Neurosciences & Neurology) and the College of Arts and Sciences (Psychological Sciences)
NEUR 166 Explorations in Neuroscience (1 credit, Tues, 2:30 – 3:20)
This survey course provides students with an opportunity to learn about some of the most exciting and timely concepts in neuroscience, including topics in basic and translational/medical research, as well as perspectives on neuroscience as a profession, through a series of 14 lectures given by members of the Neurosciences Department in the Case Western Reserve University School of Medicine. Topics are presented in a way that can be understood by students who have taken a high school biology class. Every effort is made to explain any new concepts that are included in the lectures. Each lecturer will provide general background reading material for the topics they discuss.
Taught by faculty from the Neurosciences Department in the School of Medicine
Dr. Peng Zhang will join us as new Assistant Professor in January 2020!
Dr. Peng Zhang obtained PhD from SUNY Upstate Medical University and is currently a postdoc in Dr. Ann Marie Craig’s lab at the University of British Columbia, Canada. He studies neural development, in particular synapse formation. He has received a SFARI Bridge to Independent Award.
Dr. Masashi Tabuchi will join us us a new Assistant Professor in January 2020!
Dr. Masashi Tabuchi will be our new Assistant Professor, January 2020. Dr. Masashi Tabuchi studies neural circuit of arousal, sleep and hunger using Drosophila as a model. He is coming to Case from Johns Hopkins School of Medicine where he is a postdoc in Dr. Mark Wu’s lab. Dr. Tabuchi is a recipient of a K99/R00 grant from NIH.
By: UPI | Health News| Published: November 27, 2018
Scientists stimulate breathing, forelimb movement in rats with spinal injuries
Six months later, the treatment restored complete diaphragm and partial forelimb function on the severed side of the rats spines. Photo by lculig/Shutterstock
A new treatment could restore breathing and limb function to millions of people worldwide living with chronic spinal cord injuries.
Researchers of a new study published Tuesday in the journal Nature Communications focused on treating axons, cells that can regenerate nerve extensions in a damaged spinal cord.
"For the first time we have permanently restored both breathing and some arm function in a form of high cervical, chronic spinal cord injury-induced paralysis. The complete recovery, especially of breathing, occurs rapidly after a near lifetime of paralysis in a rodent model," Jerry Silver, professor of neurosciences at Case Western Reserve University School of Medicine and study senior author, said in a press release.
Scientists injected the chondroitinase enzyme into the severed spinal cords of rats. The enzyme clears out inhibitory molecules freed axons up to help speed up the regeneration process
"The strategy was to use a simple, one-time injection of an enzyme, chondroitinase, that breaks down the inhibitory proteoglycan molecules. The enzyme was administered, not within the lesion itself, but lower down within the spinal cord where motor nerve cells reside that send axons out to the diaphragm and forearm," Silver said.
The researchers say that rats treated immediately after spinal injury only got a minor benefit compared to animals with chronic spinal cord damage.
Overall, 70 percent of the rats could use their forelimbs to move around and 60 percent saw improved diaphragm function.
Six months later, the treatment restored complete diaphragm and partial forelimb function on the severed side of the rats spines.
"Our data illustrate the relative ease with which an essential motor system can regain functionality months to years after severe spinal cord injury," Silver said. "The treatment regimen in our study is relevant to multiple types of chronic incomplete spinal traumas, and we are hopeful it may also help restore motor function following spinal cord injury in humans."