The hippocampus is a brain area fundamental for cognitive functions, such as learning, memory, spatial navigation and emotion regulation, and is mainly affected in Alzheimer’s disease (AD). AD is an irreversible neurodegenerative disease, characterized by pathological protein aggregations and cognitive impairments. To date, there is no treatment for Alzheimer’s disease. The search for a therapy is urgently needed to alleviate the suffering of patients and relieve the burden on society. Neural stem cells (NSCs) in the hippocampal neurogenic niche sustain continuous neurogenesis in adulthood. Adult hippocampal neurogenesis (AHN) is functionally associated with many cognitive and emotional functions in humans and rodents. In particular, hippocampal neurogenesis is impaired in AD patients and AD mouse models and may be a putative therapeutic target for curing AD. In my project, endogenous hippocampal neurogenesis is manipulated in the 3xTg AD mouse model by a chronic, genetically-driven expansion of hippocampal NSCs. Exploiting intrinsic NSCs potential to generate newborn neurons increases the neurogenesis in 3xTg AD mice. The boosted neurogenesis ameliorates the anxiety-like behavior, improves spatial navigational performances and restores the connectivity of the hippocampal network in AD. Altogether, this study demonstrates the beneficial effect of enhancing neurogenesis by exploiting the endogenous NSCs reserve to rescue AD phenotypes and elucidates the functional contribution of neurogenesis to learning and memory. The findings support and highlight the therapeutic potential of enhancing neurogenesis in the treatments of neurodegenerative diseases.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89083 |
| Date | 17 January 2024 |
| Creators | Lee, Chi-Chieh |
| Contributors | Kempermann, Gerd, Arenas, Ernest, Technische Universität Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
Page generated in 0.0021 seconds