Author: Bo Peng Lear

Publisher:

Published: 2023

Total Pages: 0

ISBN-13:

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When the mammalian central nervous system (CNS), the brain and spinal cord, is damaged or degenerates, there is limited to no regeneration, leading to permanent and debilitating functional impairments resulting in high rates of mortality. Neural repair is so difficult because of both the inhibitory environment and the lack of intrinsic potential to regenerate which is further exacerbated with aging. Even with decades of scientific studies, our understanding of how to make the CNS regenerate is still unknown. Scientists have been testing different methods to increase neural repair, either exogenous or endogenous. Exogenous repair, such as transplanting induced pluripotent stem cell (iPSC)-derived or fetal tissue-derived neural progenitors into the brain or spinal cord, can be used to replace injured neurons. Separately, endogenous regeneration, such as replenishing neurons in cases of traumatic or neurodegenerative neurological diseases from stem cells in neurogenic niches lining the ventricles and the hippocampus, can be harnessed to replace from within. Additionally, when there is damage to the neuron's projections, as in the case of spinal cord injury, the neuron could be endogenously enhanced to regenerate its axon to regain function. However, many of these potential regenerative options are still clinically unproven to be effective as therapy for neural repair. To address these knowledge gaps, my thesis investigates two different avenues of enhancing mammalian CNS regeneration. In the first two chapters of my thesis, I explore the molecular drivers that result in limited human spinal cord regeneration post injury. Decades of rodent research still have not yielded a feasible therapeutic target for CNS axon regeneration. Here, I present a novel mechanism of a nucleosome remodeler protein being an important human-specific, age-related driver of endogenous axon regeneration. In the latter two chapters using mouse models, I explore molecular methods to enhance hippocampal neuronal regeneration using the brain's endogenous neural stem cell (NSC) supply. Despite having been 7 decades since the discovery of the existence of adult mammalian NSCs, we still no do not have a clinical treatment to replace neurons in the adult brain from endogenous NSCs. Here, I present a novel mechanism of using post-transcriptional regulation to encourage neurogenesis using adult mouse in vitro and in vivo model systems. Together these data provide two different perspectives on the molecular targets of neural repair, with the goals of enhancing endogenous mammalian CNS regeneration.

Download or read book Adult Mammalian Central Nervous System Regeneration written by Bo Peng Lear and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: When the mammalian central nervous system (CNS), the brain and spinal cord, is damaged or degenerates, there is limited to no regeneration, leading to permanent and debilitating functional impairments resulting in high rates of mortality. Neural repair is so difficult because of both the inhibitory environment and the lack of intrinsic potential to regenerate which is further exacerbated with aging. Even with decades of scientific studies, our understanding of how to make the CNS regenerate is still unknown. Scientists have been testing different methods to increase neural repair, either exogenous or endogenous. Exogenous repair, such as transplanting induced pluripotent stem cell (iPSC)-derived or fetal tissue-derived neural progenitors into the brain or spinal cord, can be used to replace injured neurons. Separately, endogenous regeneration, such as replenishing neurons in cases of traumatic or neurodegenerative neurological diseases from stem cells in neurogenic niches lining the ventricles and the hippocampus, can be harnessed to replace from within. Additionally, when there is damage to the neuron's projections, as in the case of spinal cord injury, the neuron could be endogenously enhanced to regenerate its axon to regain function. However, many of these potential regenerative options are still clinically unproven to be effective as therapy for neural repair. To address these knowledge gaps, my thesis investigates two different avenues of enhancing mammalian CNS regeneration. In the first two chapters of my thesis, I explore the molecular drivers that result in limited human spinal cord regeneration post injury. Decades of rodent research still have not yielded a feasible therapeutic target for CNS axon regeneration. Here, I present a novel mechanism of a nucleosome remodeler protein being an important human-specific, age-related driver of endogenous axon regeneration. In the latter two chapters using mouse models, I explore molecular methods to enhance hippocampal neuronal regeneration using the brain's endogenous neural stem cell (NSC) supply. Despite having been 7 decades since the discovery of the existence of adult mammalian NSCs, we still no do not have a clinical treatment to replace neurons in the adult brain from endogenous NSCs. Here, I present a novel mechanism of using post-transcriptional regulation to encourage neurogenesis using adult mouse in vitro and in vivo model systems. Together these data provide two different perspectives on the molecular targets of neural repair, with the goals of enhancing endogenous mammalian CNS regeneration.