Strychni Semen Improves Spatial Memory and Promotes Axon Regeneration Following Vascular Dementia in Mice

Introduction Vascular dementia (VaD) is a cognitive disorder caused by cerebrovascular lesions, often accompanied by secondary axonal damage. Given the high energy-consuming nature of neurons, efficient mitochondrial transport is essential for providing sufficient energy for axonal regrowth. However, developing drugs that effectively modulate mitochondrial transport and support axonal regeneration following VaD remains a challenge. Methods Bilateral carotid artery stenosis (BCAS) was induced in mice, and cognitive function was assessed using the Morris water maze test. Axonal regeneration was quantified via anterograde viral tracing and immunofluorescence. The oxygen-glucose deprivation (OGD) model was established in primary cortical neurons. Axonal elongation and mitochondrial motility were evaluated using live-cell imaging. Western blotting and molecular docking techniques were applied to decipher the molecular mechanisms. Results Our study found that Strychni Semen and its active compound, strychnine (but not brucine), improved cognitive function and promoted axonal regeneration in mice subjected to BCAS. Strychnine promotes post-OGD axonal mitochondrial transport, and inhibiting mitochondrial transport blocks its axon regeneration-promoting effects. Moreover, strychnine augmented the translocation of several transporter proteins to mitochondria. Molecular docking studies further indicate that the proteins DISC1 and FEZ1 may play pivotal roles in strychnine-induced mitochondrial transport. Discussion This study provides preliminary evidence supporting the therapeutic potential of Strychni Semen and its active compound, strychnine, in axonal regeneration and VaD, although the underlying molecular machinery requires further elucidation. Conclusion Our results indicate that Strychni Semen and its active compound, strychnine, encourage axonal regeneration following VaD in mice by enhancing axonal mitochondrial transport.