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 Cholesterol-lowering drugs may fight infectious disease
22.08.2017 | Duke University

nachricht Once invincible superbug squashed by 'superteam' of antibiotics
22.08.2017 | University at Buffalo

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Cholesterol-lowering drugs may fight infectious disease

22.08.2017 | Health and Medicine

Meter-sized single-crystal graphene growth becomes possible

22.08.2017 | Materials Sciences

Repairing damaged hearts with self-healing heart cells

22.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>