Neurons that mature too quickly underlie brain pathologies, particularly human intellectual disability. At first glance, it might seem counterintuitive. Instead it is the important result obtained from a study conducted by Claudia Lodovichi‘s team, Principal Investigator at VIMM and researcher at the Institute of Neuroscience (CNR), just published in PNAS-Proceedings of the National Academy of Sciences. In particular, these are the GABAergic inhibitory neurons, ie the subset of brain cells that uses the neurotransmitter GABA to “turn off” the nerve impulse. The technique used in the study is two-photon real-time imaging.
Basically, the formation of inhibitory neurons occurs mainly during embryonic life. However, a small, but fundamental, part of the neurogenesis process occurs in the postnatal period in specific brain areas: the walls of the lateral ventricles. “The precursors of inhibitory neurons (neuroblasts) – explains Claudia Lodovichi – migrate from this area to the olfactory bulb, the area of the brain responsible for processing olfactory perceptions, and to many other cortical and subcortical areas, such as the prefrontal cortex: essential for cognitive, social, planning and control functions “. Alterations in the development and migration of these neurons can therefore lead to neurocognitive deficits.
The genetic mutation
“With my collaborators – continues Lodovichi – we studied the impact of the mutation of the gene coding Oligophrenin 1 (OPHN1), associated with human intellectual disability, on the migration of inhibitory neurons generated in the post-natal period. Aspects such as the slower speed and the alteration of the directionality of this migration are associated with specific neuronal deficits. In particular, the speed is significantly reduced due to altered responses to GABA, which plays a role in the regulation of neuroblast migration ”.
However, through specific pharmacological treatments, which block the pathways responsible for the remodeling of neuroblasts, the researchers managed to restore the correct neurogenesis process in experimental models. “Despite the complexity of intellectual disability and pathologies such as autism – Lodovichi emphasizes – these basic research studies are essential for understanding the neuronal mechanisms underlying them and for identifying the targets towards which effective therapies can be directed”.
The work, supported by the Telethon Foundation, the Armenise Harvard Foundation and the NANOMAX project of the Ministry of Education, University and Research – National Research Council, saw the collaboration with the CNR Institute of Nanosciences and the National Enterprise laboratory for nanoScience and nanoTechnology-Scuola Normale Superiore of Pisa, the Department of Biomedical Sciences of the University of Padua, the VIMM Institute of Padua, the Italian Institute of Technology of Genoa and the Irccs Institute- University of Life and Health San Raffaele of Milan.