For several years, the relationship between genetic defects at the synapses in the brain and neurodevelopmental disorders characterized by cognitive deficits has been recognized. However, a percentage of those diseases has no clear genetic causes.
A study carried out by Humanitas and Institute of Neuroscience of the Cnr, in collaboration with the Universidad Miguel Hernández Instituto de Neurociencias, for the first time identifies the relationship between high levels of inflammation and increased expression of MeCP2, a protein involved in child neurodevelopmental disorders, such as Rett syndrome and MECP2 duplication syndrome, characterized by severe physical and mental disabilities.
Michela Matteoli, director of the Cnr Institute of Neuroscience and Humanitas Neuro Center and Professor of Pharmacology at Humanitas University, explains: "We have shown that excessive inflammation increases the neuronal levels of MeCP2, a protein involved in neurodevelopmental diseases. By blocking the inflammatory cascade through an antagonist of interleukin-1 beta receptor, an anti-inflammatory drug already used in clinical practice, we were able to correct the levels of MeCP2 as well as many of the synaptic failures, normalizing the learning defects." It is a discovery made in the laboratory for which, at present, there is still no clinical evidence.
To better understand the origin of cognitive disability, even in the absence of a clear genetic cause, researchers have focused on inflammation as a major factor already known to modify the risk and severity of developmental disorders. In particular, they wanted to determine whether and how the inflammation hits the synapses, generating conditions typical of 'synaptopathies', i.e. diseases of the synapses, a term with which neurodevelopmental diseases are currently called. "The development of synaptopathies”, continues Matteoli, who led the study published in the prestigious journal eLife, “leads to defects of synapse functions, which in turn impact several abilities, including learning, attention, perception and decision making. Therefore it is essential to identify factors, genetic or otherwise, that can impair their function".
“This important discovery”, concludes Alberto Mantovani, scientific director of Humanitas and professor of Humanitas University, among the authors of the study, “could help to reduce cognitive disabilities and improve the quality of life in young patients with an autoinflammatory disease characterized by cognitive deficits".
Who: Institute of neuroscience, Humanitas, Universidad Miguel Hernández lnstituto de Neurociencias
Publications: Lack of IL-1R8 in neurons causes hyperactivation of IL-1 receptor pathway and induces MECP2-dependent synaptic defects, eLife, http://dx.doi.org/10.7554/eLife.21735
For informations: Michela Matteoli, In-Cnr, ph. 02/50316963, e-mail: email@example.com
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