Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mouse model of Rett Syndrome displays reduced cortical activity

23.08.2005


Sacha Nelson of Brandeis University in Waltham, MA and Rudolf Jaenisch of the Whitehead Institute of Biomedical Research in Cambridge, MA and their colleagues report online today in the Proceedings of the National Academy of Sciences Early Edition that spontaneous neuronal activity is reduced in the cortex of a knockout mouse model for the childhood neurodevelopmental disorder, Rett Syndrome. The Rett Syndrome Research Foundation (RSRF) and the McKnight Foundation funded this project.



Rett Syndrome (RTT) is a severe neurological disorder diagnosed almost exclusively in girls. Children with RTT appear to develop normally until 6 to 18 months of age, when they enter a period of regression, losing speech and motor skills. Most develop repetitive hand movements, irregular breathing patterns, seizures and extreme motor control problems. RTT leaves its victims profoundly disabled, requiring maximum assistance with every aspect of daily living. There is no cure.

The nervous system consists of billions of neurons that communicate with each other. Neurons don’t touch and the gap between them is called a synapse. This gap is bridged by neurotransmitters that are released by the generation of electrical signals. Some neurotransmitters are excitatory and increase activity in the brain and others are inhibitory and decrease activity. In healthy brains, a balance between excitation and inhibition is essential for nearly all functions, including representation of sensory information, cognitive processes such as decision making, sleep and motor control.


The electrical signals that neurons generate can be measured using microelectrodes. Using a technique called, whole cell patch clamp, Vardhan Dani, a graduate student in Dr. Nelson’s lab and Qiang Chang a post doctoral fellow from Rudolf Jaenisch’s lab tested the electrical impulses in the cortex of the Rett Syndrome knockout mouse model. The cortex is one of the regions of the brain affected in patients with RTT. These mice are genetically manipulated so they lack the "Rett gene", MECP2. Like individuals with Rett Syndrome, they are seemingly normal at birth and begin to exhibit Rett-like behaviors by 5 weeks of age.

Interestingly, the groups found that the excitatory-inhibitory balance in the cortex of the mice was shifted towards inhibition (decreased brain activity). They surmise that this shift toward inhibition in the cortex and perhaps other brain regions could underlie some of the cognitive, motor, linguistic and social symptoms seen in RTT.

The spontaneous firing of L5 pyramidal neurons in 5 week-old mice was decreased 4-fold when compared to normal mice. This reduction is progressive, since two weeks earlier, in presymptomatic mice, the reduction was only 2-fold. This finding represents the first experimental evidence for a physiological abnormality that exists before symptoms appear.

"It’s important to note that since this defect is seen so early it suggests that the reduced cortical activity may be a primary cellular defect that may lead to other neuropathologies," shared Qiang Chang, co-first author on the paper.

Future work will focus on elucidating the mechanisms by which the lack of MECP2 leads to increased inhibition and reduced excitation. "The next step is to use a technique called paired recording to look at the properties of individual synaptic connections between pairs of cortical neurons to find out more precisely which connections change and how. We are also trying to understand which other neural genes are regulated by Mecp2 by measuring gene expression in neurons from knockout mice and their normal siblings," said Sacha Nelson, the corresponding author of the paper.

Monica Coenraads | EurekAlert!
Further information:
http://www.rsrf.org

More articles from Health and Medicine:

nachricht Satellites, airport visibility readings shed light on troops' exposure to air pollution
09.12.2016 | Veterans Affairs Research Communications

nachricht Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>