<p>Osteogenesis imperfecta (OI) is a rare genetic disorder with heterogenous clinical severity, primarily caused to collagen I (COL1) defects. The unifying hallmark of OI pathophysiology is the presence of collagen I defects. Collagen I is one of the main components of the extracellular matrix (ECM) and in the central nervous system (CNS) defines brain architecture, supports the vascularisation and regulates crucial processes such as neuronal differentiation, migration, axonal growth and synaptogenesis. Previous findings highlighted the presence of cerebellar alterations in aged <i>Brtl</i> mice, a well-characterised murine model of dominant OI. The aim of the present work was to further investigate wheather a collagen I defect impacts CNS morphology and redox homeostasis. Morphology and redox potential were investigated in 18-month-old <i>Brtl</i>^+/− mice of both sexes, with a specific focus on the motor cortex and striatum, two regions that communicate with the cerebellum as part of the brain’s motor network. Through the application of bright-field microscopy, histological assessments were carried out using Nissl staining and Woelcke’s haematoxylin, while redox homeostasis was evaluated analysing the expression of several oxidative stress markers. Moreover, transmission electron microscopy was employed to further evaluate the impact of oxidative damage in presence of collagen I alterations on both neural and non-neural cell ultrastructure in the brains of <i>Brtl</i> mice. Overall, the cortical and striatal morphological alterations, the marked redox dysfunctions, as well as the ultrastructural changes, suggest that chronic oxidative stress, in presence of collagen I alteration, may result in morphological, ultrastructural and molecular modifications of the brain’s motor areas, paving the way for further research in this poorly investigated field.</p> Graphical abstract <p></p>