Monday February 15 2010
Scan showing an X chromosome with fragile X syndrome (purple)
“A genetic defect that causes children to dislike being hugged and sometimes reject all physical affection is closer to being understood following research into the sensory part of the brain,” The Times reported.
This story is based on a study in a mouse 'model' of fragile X syndrome, examining the area of the brain involved with processing touch. It found that newborn mice with fragile X syndrome showed subtle differences in the activity of neurones (nerve cells) during the period they were learning how to use their whiskers to sense touch. It also found it took longer for the sensory part of their brains to develop.
This is valuable and insightful research but is based on a mouse model and it is too soon to know whether its findings have direct relevance to fragile X syndrome in humans. Further study is needed to see whether these findings are relevant to understanding how human brains respond to touch.
Where did the story come from?
This research was carried out by Dr Emily Harlow and colleagues at Northwestern University, US, and the University of Edinburgh, Scotland. The study was funded by the FRAXA research foundation, Autism Speaks and the Brain Research Foundation. The paper was published in the peer-reviewed journal Neuron.
What kind of research was this?
This research investigated changes to the brain in a mouse model of fragile X syndrome.
Fragile X syndrome is the most common cause of genetically inherited mental learning disability. It is more common in boys than girls and is often associated with autism. The condition is caused by the loss of a protein called the fragile X mental retardation protein (FMRP). Loss of this protein causes a change in the shape of neurones (nerve cells) in the brain. The researchers wanted to see how these changes affected the activity of the neurones.
What did the research involve?
This research was in a group of normal mice and a group of mice that were genetically engineered to lack the Fmr1 gene and so lacked the FMRP protein.
The researchers focused on neurones in a mouse’s brain that communicate the touch sensations that it receives from its whiskers. Mice learn how to use their whiskers in the first few weeks of life. When a whisker is touched, the neurones fire and make strong connections with nearby neurones. Over time, the neurones receiving information from each whisker make connections with the nearby neurones.
The time in which the brain maps the distribution of these connections is called the ‘critical period’. During the critical period the neurones are described as ‘plastic’, where their shape and the strength of their connections are flexible and dependent on how active they are. After the critical period, the neurones are more fixed.
The researchers looked at the proteins and the pattern of the brain maps in mice up to 21 days old. They measured the amount of FMRP in normal mice when they were four and seven days old (within the critical period) and after the critical period when the mice were 21 days old.
They also examined and measured the activity of neurones connecting the thalamus (part of the brain that relays sensory information) to the cortex (which further processes and allows conscious perception of the sensory information).
What were the basic results?
The researchers found that the newborn control mice had FMRP in their neurones at four days and this increased during the critical period up to 14 days. After 21 days the relative amounts of FMRP was lowered. This suggests that FMRP is needed during the critical period of the development of these neurones.
In mice genetically engineered to lack the FMRP protein, there were changes in the activity of the neurones during the 'whisker-mapping' period. The activity of neurones depends on the activity of proteins called receptors on their surface. The change in activity of neurones in the genetically engineered mice appeared to be because of changes in how the receptors were working together to pass on the information. After seven days, these activity patterns reverted to those seen in the control mice.
During the whisker-mapping period, there was an increase in levels of one type of receptor, called the NMDA receptor, in the genetically modified mice.
In these mice, the neurones continued to have the type of activity needed to build strong connections for longer than the control mice, suggesting that the neurones took longer to mature.
Despite these differences in the activity of their neurones, mice that did not have the FMRP protein had the same pattern of whisker maps as the control mice.
How did the researchers interpret the results?
The researchers conclude that the precise timing of critical periods during brain development is essential for the proper organisation of synaptic connections and circuits. They suggest that a delayed timing of this brain organisation could lead to a change in brain circuits that persist throughout life and could contribute to how people with fragile X syndrome process sensory information.
This animal study found subtle differences in neurone activity and brain development in mice with fragile X syndrome compared to normal mice.
This is valuable and insightful research, but is based on a mouse model and it is too soon to know whether its findings have direct relevance to fragile X syndrome in humans. The study focused on neurone activity in newborn mice in the critical period when they were learning how to use their whiskers to sense touch. It is not clear whether humans have similar critical periods for learning how to respond to touch and when this development would occur. More research is needed.