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Analysis of Adult Hippocampal Neurogenesis in Neurodegenerative disease / GANG HAN

Swansea University Author: GANG HAN

DOI (Published version): 10.23889/SUthesis.62147

Abstract

Neurodegenerative diseases cause severe health and social problems. They create a health and economic burden on individuals and their families. Currently, there is no efficient treatment, apart from some attenuating medicines, for the majority of neurodegenerative diseases. Neurone loss is a consist...

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Published: Swansea 2022
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
Supervisor: Davies, Jeff ; Morgen, Alwena
URI: https://cronfa.swan.ac.uk/Record/cronfa62147
first_indexed 2022-12-08T14:37:49Z
last_indexed 2023-01-13T19:23:24Z
id cronfa62147
recordtype RisThesis
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spelling 2022-12-08T14:47:30.6483480 v2 62147 2022-12-08 Analysis of Adult Hippocampal Neurogenesis in Neurodegenerative disease 721a4a813da945ed22115eade47c8359 GANG HAN GANG HAN true false 2022-12-08 Neurodegenerative diseases cause severe health and social problems. They create a health and economic burden on individuals and their families. Currently, there is no efficient treatment, apart from some attenuating medicines, for the majority of neurodegenerative diseases. Neurone loss is a consistent characteristic of these diseases. The hippocampal dentate gyrus is one of the regions in the adult mammalian brain capable of generating new neurones throughout life. The neurogenic niche appears to play an important role in the neuronal dysfunction associated with neurodegeneration. However, the detailed mechanisms underpinning this process are still unclear. To explore the neurogenic niche in Frontal Temporal Dementia (FTD) and Parkinson’s disease (PD) we investigated disease-relevant rodent models and donated post-mortem human brain samples. Immunohistochemistry and immunofluorescent assays were developed to allow the quantification of dividing cells and immature neurones in the adult hippocampus of selected tissues. The TDP43-Q331K knock-in mice, a model of FTD, revealed a significant reduction in the number of dividing cells (Ki67+) and immature neurones (Dcx+). Distinct morphological stages of immature neurone development were observed in this disease model. Further rodent neurotoxin-based models were used to characterise neurogenesis in PD. However, contrary to previous reports, these models did not consistently induce significant deficits in adult hippocampal neurogenesis (AHN). Human post-mortem brain samples were used to explore the neurogenic niche, but we were unable to consistently observe immature neurones in non-diseased brain samples. In summary, this project identified significant AHN deficits in the FTD mouse model. These require further analysis to determine their function and possible role in human disease. E-Thesis Swansea Neurogenesis, Neurodegenerative disease 6 12 2022 2022-12-06 10.23889/SUthesis.62147 COLLEGE NANME COLLEGE CODE Swansea University Davies, Jeff ; Morgen, Alwena Doctoral Ph.D 2022-12-08T14:47:30.6483480 2022-12-08T14:35:09.1128760 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine GANG HAN 1 62147__26043__44208923bdd042dba431a1382878793e.pdf Han_Gang_PhD_Thesis_Final_Redacted_Signature.pdf 2022-12-08T14:41:25.1868297 Output 4465089 application/pdf E-Thesis – open access true Copyright: The author, Gang Han, 2022. true eng
title Analysis of Adult Hippocampal Neurogenesis in Neurodegenerative disease
spellingShingle Analysis of Adult Hippocampal Neurogenesis in Neurodegenerative disease
GANG HAN
title_short Analysis of Adult Hippocampal Neurogenesis in Neurodegenerative disease
title_full Analysis of Adult Hippocampal Neurogenesis in Neurodegenerative disease
title_fullStr Analysis of Adult Hippocampal Neurogenesis in Neurodegenerative disease
title_full_unstemmed Analysis of Adult Hippocampal Neurogenesis in Neurodegenerative disease
title_sort Analysis of Adult Hippocampal Neurogenesis in Neurodegenerative disease
author_id_str_mv 721a4a813da945ed22115eade47c8359
author_id_fullname_str_mv 721a4a813da945ed22115eade47c8359_***_GANG HAN
author GANG HAN
author2 GANG HAN
format E-Thesis
publishDate 2022
institution Swansea University
doi_str_mv 10.23889/SUthesis.62147
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description Neurodegenerative diseases cause severe health and social problems. They create a health and economic burden on individuals and their families. Currently, there is no efficient treatment, apart from some attenuating medicines, for the majority of neurodegenerative diseases. Neurone loss is a consistent characteristic of these diseases. The hippocampal dentate gyrus is one of the regions in the adult mammalian brain capable of generating new neurones throughout life. The neurogenic niche appears to play an important role in the neuronal dysfunction associated with neurodegeneration. However, the detailed mechanisms underpinning this process are still unclear. To explore the neurogenic niche in Frontal Temporal Dementia (FTD) and Parkinson’s disease (PD) we investigated disease-relevant rodent models and donated post-mortem human brain samples. Immunohistochemistry and immunofluorescent assays were developed to allow the quantification of dividing cells and immature neurones in the adult hippocampus of selected tissues. The TDP43-Q331K knock-in mice, a model of FTD, revealed a significant reduction in the number of dividing cells (Ki67+) and immature neurones (Dcx+). Distinct morphological stages of immature neurone development were observed in this disease model. Further rodent neurotoxin-based models were used to characterise neurogenesis in PD. However, contrary to previous reports, these models did not consistently induce significant deficits in adult hippocampal neurogenesis (AHN). Human post-mortem brain samples were used to explore the neurogenic niche, but we were unable to consistently observe immature neurones in non-diseased brain samples. In summary, this project identified significant AHN deficits in the FTD mouse model. These require further analysis to determine their function and possible role in human disease.
published_date 2022-12-06T14:26:40Z
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score 11.247077

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