A study led by the EHU’s Neuropsychopharmacology group provides new insights into understanding the origins of schizophrenia. The research, led by the EHU lecturer Leyre Urigüen, revealed alterations in the extracellular matrix, the “scaffolding” that supports neurons, and in the synapses, the points of communication between the neurons, thus reinforcing the idea that this is a neurodevelopmental disorder.
This study, published in Molecular Psychiatry, used a pioneering model based on neural stem cells obtained from the nasal cavity of patients with schizophrenia, more specifically, from the olfactory epithelium.
The olfactory epithelium is a region very close to the brain located at the top part of the nostrils, where the olfactory neurons that allow us to smell are located. The olfactory epithelium also contains neural stem cells that can be extracted by means of nasal exfoliation.
This simple, non-invasive method enables the extracted neural stem cells to be cultured in the laboratory and grouped together to form structures called neurospheres that mimic the initial stages of neurodevelopment, which is the process of growth, maturity and functional development of the nervous system. The process begins during pregnancy and continues until adulthood, enabling cognitive, motor and social skills to be acquired.
“That way, we got a unique window to study the disease directly and in a personalized way,” explained Paula Unzueta, the article’s lead author.
In fact, the researchers discovered that when neurospheres were generated, alterations were already taking place in genes related to the extracellular matrix. In addition to neurospheres, mature neurons can also be obtained from neural stem cells in the olfactory epithelium, and in these neurons, they also detected defects in genes linked to synapses and their interaction with the matrix.
To validate these results, the team measured, in parallel, the levels of certain proteins present in neurons cultured in the laboratory and in post-mortem brain tissue from subjects with schizophrenia. When comparing these levels with those of individuals without schizophrenia, they found that three proteins essential for the formation and functioning of synapses, L1CAM, NPTXR and SCG2, were reduced.
Dr. Urigüen stressed that “these findings link neurodevelopmental alterations to specific molecular changes in schizophrenia, and demonstrate that this cell model opens the door to discovering new biomarkers and advancing towards more personalized therapies, not only for schizophrenia, but also for other neuropsychiatric and neurodegenerative diseases.”
More information:
Paula Unzueta-Larrinaga et al, Extracellular matrix dysfunction and synaptic alterations in schizophrenia, Molecular Psychiatry (2025). DOI: 10.1038/s41380-025-03154-2
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