Seminar in Pairs: 'Maladaptive plasticity related to early movement restriction in rats to better understand neurodevelopmental disorders' and 'Early predictive biomarkers for abnormal brain development induced by fetal growth restriction'

J-Olivier Coq: ‘Maladaptive plasticity related to early movement restriction in rats to better understand neurodevelopmental disorders’

Children with neurodevelopmental disorders usually exhibit gross to fine sensorimotor impairments, reduced physical activity and altered interactions with people and the environment. These disorders may co-exist with hyperactivity, cognitive deficits, executive dysfunctions and learning impairments. In a series of studies in rats, we demonstrated that limited amounts and atypical patterns of movements, and abnormal somatosensory feedback during early movement restriction induced in adulthood degraded postural and locomotor abilities, musculoskeletal histopathology including muscle atrophy, hyperexcitability within the sensorimotor circuitry and maladaptive cortical plasticity. Such maladaptive plasticity led to a functional disorganization of the primary somatosensory and motor cortices in the absence of cortical histopathology. Early movement restriction led to early deficits in the emergence of swimming, sensorimotor reflexes and locomotor patterns and posture with toe-walking, as well as altered spontaneous activity and the development of pain. In addition, restricted rats displayed exploratory hyperactivity and impairments in object memory tasks, along with minor alterations in the histological features of the hippocampal complex. Taken all together, these results show similarities with the symptoms observed in children with neurodevelopmental disorders and thus, may contribute to explain the mechanisms underlying their emergence.

Atsuto Onoda – ‘Early predictive biomarkers for abnormal brain development induced by fetal growth restriction’

Globally, the rise in children with neurodevelopmental disorders such as autism spectrum disorder has been a matter of increasing concern. Fetal Growth Restriction (FGR) has been identified as a risk factor for neurodevelopmental disorders. However, current diagnostic technologies are inadequate for early prediction and diagnosis of brain abnormalities in FGR infants. Therefore, the present study focused on identifying biomarkers for early detection of abnormal brain development caused by FGR. This research employed a novel animal model that simulates mild, chronic intrauterine blood flow insufficiency (Kitase et al., 2020). The FGR model animals exhibited low birth weight and behavioral disorders, mirroring clinical observations. Proteomics of cerebrospinal fluid (CSF) revealed that six proteins were significantly correlated with birth weight. Out of the six proteins identified, four – Neuroserpin, Alpha2-macroglobulin, OX2 membrane glycoprotein, and Polyubiquitin-b – exhibited chronic abnormal expression in both CSF and serum. Histopathological analysis has indicated that abnormal expression of the four proteins was observed in neurons, astrocytes, and oligodendrocytes in the cortex and hippocampus. Furthermore, the injection of mesenchymal stem cells, which proved effective in mitigating brain function abnormalities induced by FGR, also suppressed the abnormal expression of these four proteins. Similar expression patterns were also observed in human serum of newborns. These results suggest that these proteins could be early predictive biomarkers and surrogate markers for FGR-related brain development abnormalities.