Effects of minocycline on vocal production and auditory processing in a mouse model of Fragile X

Effects of minocycline on vocal production and auditory processing in a mouse model of Fragile X

Khaleel Razak, PhD – University of California, Riverside with Iryna Ethell, PhD Co-Principal Investigator FRAXA Awards: $45,000 in 2016 $45,000 in 2013 $45,000 in 2012 2013 Update by Khaleel Razak, PhD The goals of our FRAXA-funded research project are to determine robust biomarkers relevant to the FXS and to examine the efficacy of minocycline treatment. We particularly focus on the symptoms related to communication from both production and reception viewpoints. We have identified multiple biomarkers in the Fmr1 knockout (KO) mice with the first year’s funding. There is a deficit in ultrasonic vocalizations (USV) in the KO mice. When male mice are paired with females, the KO males call at significantly slower rates (Rotschafer et al., 2012). Minocycline treatment during the first month of life, reverses the USV deficits. Based on this promising finding of a potentially useful pre-clinical outcome measure, we have pursued identification of critical developmental time windows

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GABAergic Inhibitory Function in Fragile X Syndrome

GABAergic Inhibitory Function in Fragile X Syndrome

With a $100,000 grant from FRAXA Research Foundation, Drs. Joshua Corbin and Molly Huntsman from the Children’s National Medical Center examined the role of a particular class of brain cells (inhibitory interneurons) that dampen excessive activity in the “emotional center of the brain” (the amydala). This inhibition is deficient in Fragile X, and so they are looked for ways to remedy this. This is particularly interesting to parents of children who are overly anxious and emotional. They worked with Dr. Walter Kaufmann, a clinician at Kennedy Krieger Institute in Maryland.

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Genome-wide Epigenetic Markers in Fragile X

Genome-wide Epigenetic Markers in Fragile X

With $155,000 in grants from FRAXA Research Foundation over several years, Dr. Miklos Toth of Cornell University discovered increased startle response in Fragile X mice and that baclofen can correct this phenotype. They also studied epigenetics (ie factors other than the gene itself) which can determine symptom severity in Fragile X.

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Therapeutic Interventions in FMR1 Knockout and Transgenic Mice: Role of the FMR1 Gene

Therapeutic Interventions in FMR1 Knockout and Transgenic Mice: Role of the FMR1 Gene

With a $229,000 grant from FRAXA Research Foundation in 2006, Drs. Richard Paylor, David Albeck, and Francis Brennan at the Baylor College of Medicine found that, in mice as in humans, the level of Fragile X protein in brain cells plays a prominent role in determining levels of activity and anxiety.

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Treatment of a Mouse Model of Fragile X Syndrome with MPEP

Treatment of a Mouse Model of Fragile X Syndrome with MPEP

With a $49,000 grant from FRAXA Research Foundation in 2003, Dr. Linda Crnic at the University of Colorado continued studies of MPEP in Fragile X mice, exploring whether chronic use ameliorates symptoms of Fragile X syndrome without impairing cognitive function.

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Prepulse inhibition in Fragile X

Prepulse inhibition in Fragile X

Alcino Silva, PhD — UCLA with Paul Frankland, PhD, FRAXA Postdoctoral Fellow University of California Los Angelos FRAXA Award: $27,000 in 1999 by Paul Frankland, 8/1/2001 Fragile X syndrome is associated with mild to severe learning disabilities, as well as attentional problems. In 1991, scientists discovered the gene (called FMR1) that causes Fragile X. In people with Fragile X, a defect in the FMR1 shuts the gene down. Like a defective factory, the FMR1 gene cannot manufacture the protein it normally makes. The gene is on strike! The discovery of the Fragile X gene lead to the development of the first Fragile X mouse model. This mutant mouse has been engineered to lack the FMR1 gene, and so, just as in people with Fragile X, no Fragile X protein is manufactured. Because the Fragile X mouse has been found to have learning difficulties, it provides a perfect test ground for

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Startle Modulation in Males with Fragile X Syndrome

Startle Modulation in Males with Fragile X Syndrome

With a $42,720 grant from FRAXA Research Foundation in 2001, Dr. Elisabeth Dykens at Vanderbilt University showed that startle and prepulse inhibition (PPI) are very much affected in young males are particularly affected by Fragile X syndrome. Results published.

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