The cerebellum and fragile X syndrome

An important discovery has been made that will significantly advance our understanding of the brain mechanisms underlying fragile X syndrome.

Fragile X syndrome is the most common inherited intellectual disability on the autism spectrum, occurring in 1 in 4,000 men and 1 in 7,000 women. Patients with fragile X syndrome suffer from multiple behavioral disorders such as cognitive deficiencies, hyperactivity, anxiety, social interaction problems and, in addition, motor deficits that affect the acquisition of fine motor skills for which there is still no effective specific treatment.

However, Ricardo Martín’s team, a professor in the Physiology Department of the Complutense University of Madrid (UCM) School of Medicine, has just publicly presented the results of a study that bring some hope for this disease.

The contacts through which neurons communicate with each other are called synapses and are sites with important metabolic and functional activity. The new study points to the abnormal increase in the number of glutamate synaptic vesicles as the cause of both long-term loss of synaptic plasticity in synapses between parallel fibers and cerebellar Purkinje cells, as well as learning disabilities. motor and social deficits in a mouse model of this syndrome.

Furthermore, these investigators demonstrate that counteracting these synaptic abnormalities by pharmacological activation of the metabotropic glutamate receptor mGluR4 improves motor learning and mitigates social deficits in this animal model of fragile X syndrome.

On the left, synapses from a normal mouse (control group). On the right, synapses from a fragile X syndrome mouse model. It can be clearly seen that the fragile X syndrome model mouse has more synaptic vesicles in contact with the presynaptic membrane. (Photos: UCM)

The study is titled “The activation of mGluR4 rescues parallel fiber synaptic transmission and LTP, motor learning and social behavior in a mouse model of Fragile X Syndrome”. And it has been published in the journal Molecular Autism.

The Pablo de Olavide University of Seville in Spain has also participated in the research. (Source: UCM)