2. Academic Validation
  3. Anti-RGMa neutralizing antibody ameliorates vascular cognitive impairment in mice

Anti-RGMa neutralizing antibody ameliorates vascular cognitive impairment in mice

  • Neurotherapeutics. 2025 Mar;22(2):e00500. doi: 10.1016/j.neurot.2024.e00500.
Masaya Yamamoto 1,  Takahide Itokazu 2,  Hiroki Uno 1,  Takakuni Maki 3,  Nao Shibuya 1,  Toshihide Yamashita 4
Affiliations

Affiliations

  • 1 Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Japan.
  • 2 Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Japan; Department of Neuro-Medical Science, Graduate School of Medicine, Osaka University, Suita, Japan. Electronic address: t.itokazu@molneu.med.osaka-u.ac.jp.
  • 3 Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • 4 Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Japan; Department of Neuro-Medical Science, Graduate School of Medicine, Osaka University, Suita, Japan; WPI-Immunology Frontier Research Center, Osaka University, Suita, Japan. Electronic address: yamashita@molneu.med.osaka-u.ac.jp.
PMID: 39613526 DOI: 10.1016/j.neurot.2024.e00500
Abstract

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.

Keywords

Chronic hypoperfusion; Cognitive impairment; Neurogenesis; Repulsive guidance molecule-a (RGMa).

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