Moderate 3D Orbital Shaking Mitigates Maternal Separation-Induced Neurodevelopmental Impairments In Rats

Maternal separation during early life is a well-established model for inducing neurodevelopmental impairments. Mechanical stimulation by passive movement, such as three-dimensional orbital shaking (3D-OS), has been suggested as a neuroprotective intervention in cell and tissue models, but its effects in neonatal animals remain unknown. We investigated whether 3D-OS applied during the postnatal period could attenuate neurogenesis impairments and cognitive deficits induced by maternal separation in rats. Eighteen newborn Sprague Dawley rats were assigned to control (C), maternal separation (MS), or maternal separation plus orbital shaking (MSOS) groups. Maternal separation was performed 3 h/day between postnatal days 2-21; MSOS additionally received 3D-OS stimulation (25 rpm, 3 h/day). Behavioural tests (Open Field, Novel Object Recognition, Morris Water Maze, Passive Avoidance), combined with RT-qPCR, Western blot, histology, and immunohistochemistry were conducted. MSOS rats displayed improved spatial learning in the early phases of the Morris Water Maze and recovered retention memory in Passive Avoidance compared to MS. In contrast, Open Field and Novel Object Recognition tests revealed no differences, and Western blot did not detect significant protein changes. Histological analysis showed reduced neuronal loss and vacuolisation in hippocampal and cortical regions of MSOS rats. RT-qPCR demonstrated reduced hippocampal FGF2 and FGFR1 expression in MS, partially restored by 3D-OS, while immunohistochemistry indicated increased FGFR2 and decreased FGFR1 in MSOS. Early-life 3D-OS administration alleviated maternal separation-induced cognitive decline and structural impairments, and enhanced hippocampal plasticity markers, providing preclinical evidence that moderate mechanical stimulation may support brain development and exert neuroprotective effects against early-life stress. HighlightsO_LIEarly-life 3D-OS mitigated maternal separation-induced deficits. C_LIO_LIImproved performance in Morris Water Maze and Passive Avoidance tasks. C_LIO_LINo significant effects observed in OFT, NOR, or Western blot. C_LIO_LI3D-OS restored hippocampal FGF-2 and FGFR1 mRNA levels in stressed rats. C_LIO_LIGentle mechanical stimulation may support early brain development. C_LI