Fragile X

Fragile X

Older news items (pre-2010) brought over from the old website

New method of scoring IQ tests for fragile X children

IQ tests can tell us little about the learning abilities of children with intellectual disabilities, as parents of such children know only too well. So it’s exciting to learn that a new system of scoring IQ tests has been devised for children with fragile X syndrome. This new test reflects the variability evident among learning disabled children, and tells parents, teachers and doctors how a child with fragile x syndrome deviates from the normal population in every sub-test area. The researchers also found a significant correlation between the scores and the level of FMR1 protein in the blood (the protein expressed by the normal variant of the so-called fragile X gene), and between the IQ test scores and scores on the Vineland Adaptive Behavior Composite, which measures personal and social skills used in everyday living.

[886] Reiss, A. L., Hall S., Hessl D., Nguyen D. V., Green C., Chavez A., et al.
(2009).  A solution to limitations of cognitive testing in children with intellectual disabilities: the case of fragile X syndrome.
Journal of Neurodevelopmental Disorders. 1(1), 33 - 45.

http://www.physorg.com/news148642082.html

Acne drug may help those with Fragile X syndrome

A new mouse study has found that a readily available drug called minocycline, used widely to treat acne and skin infections, helps Fragile X syndrome. Human trials have already been approved. The study has revealed that dendritic spine development is impaired in mice with Fragile X, and that this drug reduces levels of the enzymes interfering with their healthy development. The mice showed healthier dendritic spines, reduced anxiety, and improved cognition.

[863] Bilousova, T. V., Dansie L., Ngo M., Aye J., Charles J. R., Ethell D. W., et al.
(2009).  Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model.
Journal of Medical Genetics. 46(2), 94 - 102.

http://www.eurekalert.org/pub_releases/2008-10/uoc--urp100308.php

Fragile X retardation syndrome corrected in mice

In another study targeting the glutamate receptor mGluR5, researchers have fixed multiple defects in fragile X mice by reducing these receptors by 50%. They achieved this through genetic engineering, but drugs blocking mGluR5 receptors are now entering human clinical trials. Fragile X is the most common form of inherited mental retardation and a leading identified genetic cause of autism.

[1306] Dölen, Gül, Osterweil E., Rao S. B. S., Smith G. B., Auerbach B. D., Chattarji S., et al.
(2007).  Correction of Fragile X Syndrome in Mice.
Neuron. 56(6), 955 - 962.

http://www.eurekalert.org/pub_releases/2007-12/cp-fxr121407.php
http://www.eurekalert.org/pub_releases/2007-12/miot-mci121407.php

Mouse study points to new therapy for Fragile X sufferers

A mouse study has found evidence that fragile X mutation produces a highly selective impairment to long-term potentiation in hippocampal cells, and that adding brain-derived neurotrophic factor (BNDF) proteins to the hippocampus restored it.

[1064] Lauterborn, J. C., Rex C. S., Kramar E., Chen L. Y., Pandyarajan V., Lynch G., et al.
(2007).  Brain-Derived Neurotrophic Factor Rescues Synaptic Plasticity in a Mouse Model of Fragile X Syndrome.
J. Neurosci.. 27(40), 10685 - 10694.

http://www.eurekalert.org/pub_releases/2007-10/uoc--urr100507.php

Fundamental defect in fragile X syndrome identified and corrected

In an exciting new cell study, scientists have not only discovered the fundamental defect that causes fragile X syndrome (the most common inherited form of mental retardation), but also how to correct the problem. It is hoped that this will eventually lead to the development of human therapies for this previously untreatable condition.

[647] Nakamoto, M., Nalavadi V., Epstein M. P., Narayanan U., Bassell G. J., & Warren S. T.
(2007).  Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors.
Proceedings of the National Academy of Sciences. 104(39), 15537 - 15542.

http://www.eurekalert.org/pub_releases/2007-09/eu-sif091307.php

Fragile X syndrome -- A stimulating environment restores neuronal function in mice

Mice in which the gene that causes Fragile X syndrome —- the most common form of inherited mental retardation — in humans had been knocked out, showed reduced long-term potentiation in neurons due to abnormalities in the channels that regulate the flow of calcium into neurons. Excitingly, exposure to an enriched environment restored normal neuronal plasticity, suggesting that mechanisms for synaptic plasticity are in place, they just require stronger neuronal activity to be triggered.

[638] Meredith, R. M., Holmgren C. D., Weidum M., Burnashev N., & Mansvelder H. D.
(2007).  Increased Threshold for Spike-Timing-Dependent Plasticity Is Caused by Unreliable Calcium Signaling in Mice Lacking Fragile X Gene Fmr1.
Neuron. 54(4), 627 - 638.

http://www.physorg.com/news99144459.html
http://www.eurekalert.org/pub_releases/2007-05/cp-fxs051807.php

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Older news items (pre-2010) brought over from the old website

New screening tool helps identify children at risk

An exam, called the NICU (neonatal intensive care unit) Network Neurobehavioral Scale (NNNS), has been created to identify newborns who may have problems with school readiness and behavior at age four. This opens up the possibility of early intervention to prevent these problems. The screening exam has been tested on 1248 babies, mostly black and on public assistance. Five discrete behavioral profiles were reliably identified; the most extreme negative profile was found in 5.8% of the infants. Infants with poor performance were more likely to have behavior problems at age three, school readiness problems at age four, and low IQ at 4 ½ — 40% had clinically significant problems externalizing (impulsivity and acting out), internalizing (anxiety, depression, withdrawn personalities), and with school readiness (delays in motor, concepts and language skills), and 35% had low IQ.

[596] Liu, J., Bann C., Lester B., Tronick E., Das A., Lagasse L., et al.
(2010).  Neonatal neurobehavior predicts medical and behavioral outcome.
Pediatrics. 125(1), e90-98 - e90-98.

http://www.eurekalert.org/pub_releases/2009-12/bu-nst120709.php

Cognitive dysfunction reversed in mouse model of Down syndrome

Down syndrome is characterized by specific learning impairments (for example, difficulties in using spatial and contextual information to form new memories, but less difficulty at remembering information linked to sensory cues) that point to the hippocampus as a problem area. Investigation has revealed that the problem lies in degeneration of the locus coeruleus, which sends norepinephrine to neurons in the hippocampus. Now a study using genetically engineered mice has found that norepinephrine precursor drugs improved performance in the mice within a few hours. However, the effect did wear off quite quickly too. Other research has looked at acetylcholine, which also acts at the hippocampus. The present findings suggest the best medication regimen will be one that improves both norepinephrine and acetylcholine signals. Locus coeruleus degeneration is also seen in dementia; Alzheimer’s develops among those with Down syndrome at a significantly higher rate than in the general population.

Salehi, A. et al. 2009. Restoration of Norepinephrine-Modulated Contextual Memory in a Mouse Model of Down Syndrome. Science Translational Medicine, 1 (7), 7-17.

http://www.eurekalert.org/pub_releases/2009-11/sumc-nds111309.php
http://www.eurekalert.org/pub_releases/2009-11/uoc--cdr111609.php http://www.the-scientist.com/blog/display/56154/

Testing one time is not enough

A study demonstrating the perils of one-time testing gave 16 common cognitive and neuropsychological tests to groups of people ages 18-39, 50-59 and 60-97 years. The variation between scores on the same test given three times during a two-week period was as big as the variation between the scores of people in different age groups. “It's as if on the same test, someone acted like a 20-year-old on a Monday, a 45-year-old on Friday, and a 32-year-old the following Wednesday”. The study makes clear the dangers of diagnosing learning disability, progressive brain disease or impairment from head injury on the basis of testing on a single occasion. The researcher suggests we should view cognitive abilities as a distribution of many potential levels of performance instead of as one stable short-term level; that people have a range of typical performances, a one-person bell curve. It may also be that within-person variability could be a useful diagnostic marker in itself — for example, extreme fluctuations might be an early warning of mental decline.

[921] Salthouse, T. A.
(2007).  Implications of within-person variability in cognitive and neuropsychological functioning for the interpretation of change.
Neuropsychology. 21(4), 401 - 411.

http://www.physorg.com/news102689828.html
http://www.eurekalert.org/pub_releases/2007-07/apa-csv062507.php

Common cholesterol-lowering drug reverses learning disabilities in mice

Following their discovery that neurofibromatosis 1 (NF1) — the leading genetic cause of learning disabilities — is linked to dysfunction in a protein called Ras, researchers have successfully used a commonly prescribed cholesterol-lowering statin drug (lovastatin) to reverse the learning deficits in mice. Clinical trials with humans are being planned.

[1348] Li, W., Cui Y., Kushner S., Brown R., Jentsch J., Frankland P., et al.
(2005).  The HMG-CoA Reductase Inhibitor Lovastatin Reverses the Learning and Attention Deficits in a Mouse Model of Neurofibromatosis Type 1.
Current Biology. 15(21), 1961 - 1967.

http://www.eurekalert.org/pub_releases/2005-11/uoc--rf110405.php
http://www.newscientist.com/channel/health/dn8276

More light on a common developmental disorder

Chromosome 22q11.2 deletion syndrome is the most common genetic deletion syndrome, and causes symptoms such as heart defects, cleft palate, abnormal immune responses and cognitive impairments. Two related studies have recently cast more light on these cognitive impairments. Previously it was known that numerical abilities were impaired more than verbal skills. The new study found children with the chromosome deletion performed more poorly on experiments designed to test visual attention orienting, enumerating, and judging numerical magnitudes. All three tasks relate to how the children mentally represent objects and the spatial relationships among them, supporting previous arguments that such visual-spatial skills are a fundamental foundation to the later learning of counting and mathematics. The second study found that such children had changes in the shape, size and position of the corpus callosum, the main bridge between the two hemispheres.

[1139] Simon, T. J., Bearden C. E., Mc-Ginn D MD., & Zackai E.
(2005).  Visuospatial and Numerical Cognitive Deficits in Children with Chromosome 22Q11.2 Deletion Syndrome.
Cortex. 41(2), 145 - 155.

[812] Simon, T. J., Ding L., Bish J. P., McDonald-McGinn D. M., Zackai E. H., & Gee J.
(2005).  Volumetric, connective, and morphologic changes in the brains of children with chromosome 22q11.2 deletion syndrome: an integrative study.
NeuroImage. 25(1), 169 - 180.

http://www.eurekalert.org/pub_releases/2005-03/chop-lbt030205.php

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