Anti-RGMa neutralizing antibody ameliorates vascular cognitive impairment in mice

Repulsive Guidance Molecule A (RGMa) is well-recognized for its role in axon guidance. Recent studies have unveiled its diverse functions under pathological conditions within the central nervous system, such as spinal cord injury, multiple sclerosis, and Parkinson's disease. In this study, we explored the involvement of RGMa and the therapeutic effects of an anti-RGMa neutralizing antibody in a mouse model of vascular dementia (VaD). The VaD mouse model was established using the bilateral common carotid artery stenosis (BCAS) method. Immunohistochemical analysis revealed that these mice exhibited increased RGMa expression in the hippocampus, which coincided with reduced neurogenesis and impaired cholinergic innervation. These alterations manifested as cognitive impairments in the BCAS mice. Significantly, treatment with anti-RGMa neutralizing antibody reversed these pathological changes and cognitive deficits. Our findings suggest that RGMa plays a pivotal role in VaD pathology within the hippocampus and propose the anti-RGMa antibody as a promising therapeutic avenue for treating VaD.