Year: 2019
Type: dissertation
Abstract: Neurogenesis persists in the adult human hippocampus and is hypothesised to contribute to hippocampus-based memory function and emotional regulation. It has been previously reported that neurogenesis declines in normal, healthy ageing as well as Parkinson’s disease dementia (PDD). This decline in neurogenesis with age and disease may therefore be a contributing factor to the development of dementia. Recently, the established understanding of human hippocampal neurogenesis has been questioned, necessitating new approaches for measuring and analysing human neurogenesis and how it may contribute to normal hippocampal function. This thesis aimed to determine if neurogenesis gene expression is altered in the aged and PDD hippocampus and factors which may contribute to these changes. Qualitative polymerase chain reaction was used to quantify the expression of genes associated with various stages of neurogenesis from stem cell quiescence to neuronal maturation. Levels of hippocampal neurotransmitters and their metabolites were quantified using high performance liquid chromatography, and levels of hippocampal growth factors with enzyme-linked immunosorbent assay. Western blotting was used to examine expression of neurogenesis proteins. Expression of neurogenesis-related genes specific to cellular proliferation and maturation decline in both age and PDD, in-line with previous findings at the protein level in humans and other species. In contrast to previous animal studies, genes associated with neuronal maturation were more highly expressed in the anterior hippocampus than the posterior. The dopamine metabolite 3,4-dihydroxyphenylacetic acid and serotonin metabolite 5-hydroxyindoleacetic acid were associated with the pathological changes in v neurogenesis, but not the regional variability. Protein levels of growth factors associated with normal hippocampal function were also altered in the PDD hippocampus, in the absence of any apparent neuronal loss. These data suggest that neurogenesis gene expression declines in both ageing and PDD, in line with reports of reduced numbers of new neurons. Alterations in hippocampal neurotransmitters and growth factors may underlie these changes and contribute to an altered microenvironment that impacts the normal cognitive functions of the human hippocampus.
Author: Kathryn J. Mathews
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: Neuroscience Research Australia, Office of Health and Medical Research, University of New South Wales, University of Sydney, NSW Ministry of Health, Macquarie Group Foundation, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, National Institute on Alcohol Abuse and Alcoholism
OpenAlex ID: W2999107301