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What is Fragile X ?

The term Fragile X refers to a group of conditions due to defects in a gene on the X chromosome:

  • Fragile X syndrome (FXS)
  • Fragile X-associated Tremor Ataxia Syndrome (FXTAS)
  • Fragile X-associated primary ovarian insufficiency (FXPOI)

Fragile X syndrome (FXS), first known as Martin-Bell syndrome, is the most common inherited form of mental impairment. FXS affects 1 in 4,000 boys and 1 in 6,000 girls of all races and ethnic groups. While Fragile X individuals have a normal life expectancy, most will need support and care for their entire lives.

A single gene in the brain cells shuts down, causing Fragile X syndrome. In 1991, scientists discovered the defect in a gene on the X chromosome (called FMR1) that causes FXS. In affected individuals, this gene is shut down and cannot manufacture the protein it normally makes – a protein vital for normal brain development and functioning.

Large-scale population studies of Fragile X still need to be done, but it is clear that this is one of the most common genetic diseases in humans. Most people with Fragile X are not yet correctly diagnosed.

Research is aimed at developing effective treatments. In addition, this research is leading to better understanding and treatments for other conditions, such as autism, and Alzheimer’s Disease.

Grant reports

FXRFC Awards Two New Research Grants for 2010

The FXRFC has awarded two new research grants to Fragile X researchers in the laboratory of Dr. Min Zhuo, Department of Physiology, University of Toronto. This brings the total number of researchers that the FXRFC is currently funding to six, at laboratories located across the country at McGill University in Montreal, University of Toronto and University of British Columbia.

These grants have been awarded in partnership with the Canadian Institutes of Health Research (CIHR), the lead federal agency responsible for health related research in Canada. This means that the CIHR will pay for half of the total cost of  each grant for up to 3 years!

Below are brief descriptions of these new projects, as presented for you by the researchers. If you would like to explore the entire portfolio of FXRFC funded research, past and present, please click on the archives to the right.

Scientists are making significant progress in understanding Fragile X syndrome and it is a direct result of the work funded with your generous donations – please keep them coming!

2010

Principal Investigator: Dr. Min Zhuo, Ph.D., Department of Physiology, University of Toronto
Postdoctoral Fellow: Dr. Xiang Yao Li, Ph.D.
Amount: $45,000.00/year awarded in partnership with the CIHR for a period of 3 years. 
Start Date: April 1, 2010

Metabotropic glutamate receptor dependent long-term depression and calcium signals in FMR1 knockout mice

Fragile X syndrome is the most common inherited form of intellectual disability, causing cognitive impairment, behaviour abnormalities and autism. Genetic studies suggest that it is caused by the loss of an important protein called the fragile X mental retardation protein (FMRP). FMRP can regulate new protein synthesis within synapses, the key neuronal structures for brain functions such as learning and memory.  It is generally believed that the brain needs to synthesize new proteins needed for synaptic functions and memory storage. The loss of FMRP results in the misregulation of local protein synthesis, and thus impairment of brain functions. In this proposal, we propose to study learning-related synaptic changes (called LTP and LTD) in two main memory related regions, the hippocampus, and anterior cingulate cortex (ACC) of the FMRP knockout mice. 

The induction of LTD that is mediated by a key neuronal receptor (called mGluR) depends on the elevation of a calcium signal within each brain cell. It is still unclear as to how this calcium activation of the mGluRs is connected to FMRP. We hypothesize that the calcium signal is abnormal in the ACC and hippocampus of FMR1 KO mice, and we propose to study LTD and calcium signalling during LTD induction in these areas. We believe that the altered calcium signal affects the synaptic plasticity in the cortex and the underlying behavioral phenotype of FMR1 KO mice. We will also examine how an enriched environment will affect these pathways in the knockout mice, and test the effects of various drugs that alter the mGluR- LTD calcium signaling process.  The goal is to determine if the abnormal synaptic plasticity can be reversed by manipulating the calcium signal.

Principal Investigator: Dr. Min Zhuo, Ph.D., Department of Physiology, University of Toronto
Postdoctoral Fellow: Dr. Chen Tao, Ph.D.
Amount: $45,000.00/year awarded in partnership with the CIHR for a period of 2 years.
Start Date: April 1, 2010

Investigation of FMRP-related changes in dendritic morphology and intrinsic properties of ACC pyramidal cells

Fragile X syndrome (FXS) is the most common inherited form of developmental disability and autism. It is caused by the loss of the Fragile X Mental Retardation Protein (FMRP) due to the mutation of the FMR1 gene and is characterized by cognitive impairment, deficits of learning and memory, hyperactivity and anxiety. It has already been shown that the absence of FMRP may lead to the abnormal cellular branching and changes in cellular communication, while little attention has been paid to the properties of cells within the anterior cingulate cortex (ACC). Furthermore, it has not been reported whether the anatomical characteristics of cells with different electrical properties are equally affected in FXS. Thus, we propose to compare the anatomical characteristics with the electrical properties of different kinds of cells within the ACC and study the FMRP-related changes on them. 

Malformation of the ACC induces defects in fear memory.  We will examine the interaction between FMRP and environmental enrichment (EE), and the interaction of FMRP with the dopamine neurotransmitter system of the brain. We will investigate the rescuing role of EE by rearing mice in an environment that consists of a spacious cage (Habitrail) with various toys, tunnels, platforms, spin wheels and ladders for a month. The effects of the dopamine neurotransmitter system will be tested by administering a drug that stimulates the D1 receptor (D1R) and examining for any structural and electrophysiological abnormalities in the brain cells.

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