COLLAGEN, BEYOND THE SCAFFOLD: EXPLORING BRAIN VULNERABILITY IN THE <EM>BRTL</EM> MURINE MODEL

Osteogenesis imperfecta (OI) is a heterogeneous group of genetic disorders resulting from defects in collagen type I synthesis, modifications and secretion. Well-known for its skeletal implications, OI encompasses also a wide spectrum of extraskeletal symptoms. Notably, despite being poorly expressed in the adult brain, collagen plays crucial roles regulating neuronal development as well as supporting the brain’s vascularisation and architecture. In addition, mutant collagen type I may impair normal cellular homeostasis, leading to chronic cellular stress that, over time, could propagate to the tissue and systemic level.
Therefore, the aim of this work was to investigate whether collagen type I defects may alter the homeostatic balance within the brain by promoting sustained cellular stress and progressively undermining its integrity. We explored possible brain morphology alterations and modulation of specific molecular mechanisms involved in the maintenance of neuronal intracellular homeostasis in 18-month-old Brtl mice, a well-characterised murine model of dominant OI, combining histological, immunohistochemical and ultrastructural approaches.
Altogether, our results evidenced brain changes in Brtl animals, suggesting an altered neurobiological homeostasis within the CNS of mutant mice. Thus, this study supports that collagen type I dysfunctions may progressively undermine the brain’s integrity and provides new insights into the mechanisms underlying neuronal vulnerability.