Survivin enhances hippocampal neurogenesis and cognitive function in Alzheimer's disease mouse model

• Published in: CNS neuroscience & therapeutics 2024-04, Vol.30 (4), p.e14509-n/a
• Main Authors: Lee, Yeongae, Ju, Yeon‐Joo, Gee, Min Sung, Jeon, Seung Ho, Kim, Namkwon, Koo, Taeyoung, Lee, Jong Kil
• Format: Article
• Language: English
• Subjects: 5XFAD mouse; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's disease; Animals; Apoptosis; Brain research; Cell cycle; Cloning; Cognition - drug effects; Cognitive ability; Dentate gyrus; Disease Models, Animal; Embryos; Hippocampus; Hippocampus - metabolism; Laboratory animals; Mice; Mice, Transgenic; Neural stem cells; Neurodegenerative diseases; Neurogenesis; Neurogenesis - drug effects; Neurogenesis - physiology; Neuromodulation; Neurons; Original; Penicillin; Plasmids; proneural genes; Proteins; Selenium; Stem cells; Survivin; Survivin - genetics; Survivin - metabolism; Therapeutic targets
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.14509

Aims Cognitive impairment is associated with reduced hippocampal neurogenesis; however, the causes of decreased hippocampal neurogenesis remain highly controversial. Here, we investigated the role of survivin in the modulation of hippocampal neurogenesis in AD. Methods To investigate the effect of survivin on neurogenesis in neural stem cells (NSCs), we treated mouse embryonic NSCs with a survivin inhibitor (YM155) and adeno‐associated viral survivin (AAV‐Survivin). To explore the potential role of survivin expression in AD, AAV9‐Survivin or AAV9‐GFP were injected into the dentate gyrus (DG) of hippocampus of 7‐month‐old wild‐type and 5XFAD mice. Cognitive function was measured by the Y maze and Morris water maze. Neurogenesis was investigated by BrdU staining, immature, and mature neuron markers. Results Our results indicate that suppression of survivin expression resulted in decreased neurogenesis. Conversely, overexpression of survivin using AAV‐Survivin restored neurogenesis in NSCs that had been suppressed by YM155 treatment. Furthermore, the expression level of survivin decreased in the 9‐month‐old 5XFAD compared with that in wild‐type mice. AAV‐Survivin‐mediated overexpression of survivin in the DG in 5XFAD mice enhanced neurogenesis and cognitive function. Conclusion Hippocampal neurogenesis can be enhanced by survivin overexpression, suggesting that survivin could serve as a promising therapeutic target for the treatment of AD. GA Survivin is able to regulate neurogenesis in vitro and in vivo model. Our results demonstrate that therapeutic effects of survivin which improves cognitive function by enhancing neurogenesis in 5XFAD mouse. Survivin seems to be a good candidate for therapeutics to restore cognitive function in hippocampus of AD.