MicroRNA Mediated Astroglial GLT1 Dysregulation in Fragile X

Almost all brain research focuses on neurons – nerve cells. However, the brain has many more glial cells which support, nourish, and protect the neurons. FRAXA Research Foundation awarded $90,000 to support Dr. Yang’s studies of how changes in glial cells contribute to fragile X syndrome.

2017 Fragile X Research Grant: MicroRNA Mediated Astroglial GLT1 Dysregulation in Fragile X
$90,000 Grant
Yongjie Yang, PhD
Principal Investigator
Tufts University
2017 FRAXA Research Grant
$90,000 over 2 Years
Fully funded by a grant from The Pierce Family Fragile X Foundation

Glutamate is the major excitatory neurotransmitter in the brain. Abnormal regulation of glutamate has been implicated in many neuropsychiatric disorders, including autism, schizophrenia, and fragile X syndrome. It is thought that glutamate levels outside of the nerve cells are elevated and causes nerves more “excited” and induces many symptoms in humans with fragile X and also in mice bred to mimic fragile X syndrome.

Much of glutamate metabolism depends on astrocytes, the versatile and abundant cells nestled between all the neurons of the brain. Extracellular glutamate (which floats around in between brain cells) is regulated by one of the most abundant proteins in the brain, the glutamate transporter GLT1, which is expressed mainly by astrocytes. Previous studies from the Yang lab at Tufts University School of Medicine have found that there is a decrease of this critical glutamate transporter GLT1 in fragile X mice.

This group has shown that removing the fragile X protein from astrocytes decreases the astrocytes’ ability to sweep up excess glutamate. They have recently identified a few small RNA molecules called microRNA that are involved in the regulation of GLT1. With the help of this research grant, they are now exploring how these microRNAs changes underlie decreased GLT1 expression. The Yang lab is also testing whether these microRNAs can restore astrocytes’ ability to reduce extracellular glutamate levels, thus hold the potential to become new therapies for fragile X syndrome.

Haruki Higashimori

Haruki Higashimori, PhD
Co-Principal Investigator

Yuqin Men

Yuqin Men, PhD
FRAXA Fellow

Previous Grant to this Team
$80,000 in 2012-2013
Co-funded with the Autism Science Foundation

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