Featured Research

from universities, journals, and other organizations

Neurological disorder impacts brain cells differently

Date:
November 9, 2011
Source:
University of California - San Diego
Summary:
In a new paper, researchers describe in deeper detail the pathology of a devastating neurological disorder, but also reveal new cellular targets for possibly slowing its development.

In a paper published in the Nov. 9 issue of The Journal of Neuroscience, researchers at the University of California, San Diego School of Medicine and University of Washington describe in deeper detail the pathology of a devastating neurological disorder, but also reveal new cellular targets for possibly slowing its development.

Spinocerebellar ataxia type 7 (SCA7) is an inherited neurological disorder in which cells in the cerebellum and brainstem degenerate, resulting in progressive loss of physical coordination and possible blindness. Its pathology is similar to other neurodegenerative diseases like Parkinson's, Huntington's and amyotrophic lateral sclerosis. And like them, it's currently incurable.

The scientists, led by Al La Spada, MD, PhD, chief of the division of genetics in the UC San Diego department of pediatrics, and professor of cellular and molecular medicine, neurosciences and biological sciences, used a variety of transgenic mouse models to show that SCA7 results from genetic dysfunction not just in affected neurons, but also in associated non-neuronal support cells.

"The central nervous system is quite complicated, with neurons interacting with each other and with other cell types. So it shouldn't be a surprise that the disease process is similarly complex," said La Spada, who is also associate director of the UC San Diego Institute for Genomic Medicine. "We show that dysfunction in a variety of cell types contributes to SCA7, and that if you can improve function in any of these cell types, you have a reasonable chance of improving treatment of the disease."

La Spada and colleagues created a transgenic mouse in which the key gene mutation that causes SCA7 could be easily manipulated. The mouse was then bred with other mouse models that eliminated the mutant gene protein from specific cell types affected by SCA7: Purkinje neurons (large cells in the cerebral cortex responsible for motor coordination), Bergmann glia (support cells found in the cerebellum) and cells in the olivary complex (part of the brainstem controlling body movement).

By creating and comparing mice that expressed the mutant gene only in targeted cells, La Spada said the scientists made two unexpected discoveries: First, when the gene mutation was eliminated from Bergmann glia, neurodegeneration continued unabated and still involved dysfunction and degeneration of the Bergmann glia themselves. Second, when the mutation was excised from Purkinje neurons and the olivary complex, there was significantly less neurological damage and Bergmann glia remained intact.

"The first result highlights the relatively new idea that degeneration goes both ways," said La Spada. "It isn't just neurons becoming affected when their support cells dysfunction. The Bergmann glia didn't express the mutant gene, but they still degenerated. This shows the bilateral relationship between neurons and non-neuronal cells. They're equal partners, in both normal functioning and in disease.

"The second result underscores the relevance of Purkinje cells and the olivary neuron circuit in the brainstem to SCA7. When it's dysfunctional, degeneration occurs. This is crucial for our understanding of this disease, and should enable us to develop more specific therapeutic approaches. Although we have our work cut out for us, we now have a better idea of what we're up against."

Funding for this research came, in part, from the National Institutes of Health.

Co-authors of the study are Stephanie A. Furrer, Mathini S. Mohanachandran, Sarah M. Waldherr, Christopher Chang and Bryce L. Sopher, of the UCSD Department of Neurology; Vincent A. Damian, UCSD Department of Biochemistry; Gwenn A. Garden, UCSD Department of Neurology and Center on Human Development and Disability, University of Washington.


Story Source:

The above story is based on materials provided by University of California - San Diego. The original article was written by Scott LaFee. Note: Materials may be edited for content and length.


Journal Reference:

  1. S. A. Furrer, M. S. Mohanachandran, S. M. Waldherr, C. Chang, V. A. Damian, B. L. Sopher, G. A. Garden, A. R. La Spada. Spinocerebellar Ataxia Type 7 Cerebellar Disease Requires the Coordinated Action of Mutant Ataxin-7 in Neurons and Glia, and Displays Non-Cell-Autonomous Bergmann Glia Degeneration. Journal of Neuroscience, 2011; 31 (45): 16269 DOI: 10.1523/JNEUROSCI.4000-11.2011

Cite This Page:

University of California - San Diego. "Neurological disorder impacts brain cells differently." ScienceDaily. ScienceDaily, 9 November 2011. <www.sciencedaily.com/releases/2011/11/111109131823.htm>.
University of California - San Diego. (2011, November 9). Neurological disorder impacts brain cells differently. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2011/11/111109131823.htm
University of California - San Diego. "Neurological disorder impacts brain cells differently." ScienceDaily. www.sciencedaily.com/releases/2011/11/111109131823.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins