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A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
Published on: November 22, 2024
El Semen de Strychni Mejora la Memoria Espacial y Promueve la Regeneración Axonal Tras la Demencia Vascular en
Yan Zhang1, Mengting Liu1, Xinyue Zhao1,2
1Zhejiang Key Laboratory of Neuropsychopharmacology, School of Pharmaceutical Sciences, Jinhua Academy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.
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 livecell 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.
