The influence of temporal interference stimulation on neurogenesis in Alzheimer’s disease
File(s)
Author(s)
Peressotti, Sofia
Type
Thesis
Abstract
Alzheimer’s disease (AD) constitutes one of the most pressing healthcare crises to date. Hippocampal neurogenesis is significantly impaired in AD, and recent findings have shown that interventions aimed at augmenting neurogenesis could slow down cognitive decline in animal models and human patients. Chronic hippocampal deep brain stimulation (DBS) has been found to enhance cognition and ameliorate the physiopathology of AD. Although DBS holds great therapeutic potential, the invasiveness of this technique significantly hinders translation. DBS via temporally interfering (TI) electric fields has emerged as a revolutionary strategy for non-invasive brain stimulation at depth. However, its influence on the mechanisms that underlie neurogenesis in the adult brain remains largely unexplored.
This work aims to elucidate the effects of TI stimulation on neural stem cells (NSCs) and its ability to modulate neurogenic differentiation in the context of AD. A bespoke device for in vitro electrical stimulation (ES) was engineered and characterised as a stable and reproducible ES platform. This system was then used to study the neurogenic effects of three biomimetic TI stimulation paradigms (10, 40, and 100 Hz) using primary embryonic NSCs. The 10 Hz paradigm was shown to promote the expression of signalling pathways involved in neural differentiation. The neurogenic potential of TI was also evaluated in a 3D substrate, using primary neurospheres encapsulated in a bioactive self-assembling hydrogel. These results showed that the effect of ES on the neurogenic differentiation of NSCs in vitro is dependent on the dimensionality of the culture substrate. Lastly, an APPN L GF mouse model of AD was used to assess the promotion of adult neurogenesis in vivo, which showed that chronic hippocampal TI stimulation significantly increased the number of new-born neurons. This work lays the foundations for the development of novel non-invasive regenerative therapies for AD and other neurodegenerative disorders.
This work aims to elucidate the effects of TI stimulation on neural stem cells (NSCs) and its ability to modulate neurogenic differentiation in the context of AD. A bespoke device for in vitro electrical stimulation (ES) was engineered and characterised as a stable and reproducible ES platform. This system was then used to study the neurogenic effects of three biomimetic TI stimulation paradigms (10, 40, and 100 Hz) using primary embryonic NSCs. The 10 Hz paradigm was shown to promote the expression of signalling pathways involved in neural differentiation. The neurogenic potential of TI was also evaluated in a 3D substrate, using primary neurospheres encapsulated in a bioactive self-assembling hydrogel. These results showed that the effect of ES on the neurogenic differentiation of NSCs in vitro is dependent on the dimensionality of the culture substrate. Lastly, an APPN L GF mouse model of AD was used to assess the promotion of adult neurogenesis in vivo, which showed that chronic hippocampal TI stimulation significantly increased the number of new-born neurons. This work lays the foundations for the development of novel non-invasive regenerative therapies for AD and other neurodegenerative disorders.
Version
Open Access
Date Issued
2024-01-11
Date Awarded
2024-06-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Green, Rylie
Grossman, Nir
Portillo Lara, Roberto
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)