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postgraduate thesis: Investigation of synaptic degeneration as a common culprit underlying the neurodegenerative process induced by corticosterone and beta-amyloid

TitleInvestigation of synaptic degeneration as a common culprit underlying the neurodegenerative process induced by corticosterone and beta-amyloid
Authors
Advisors
Issue Date2012
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Wuwongse, S.. (2012). Investigation of synaptic degeneration as a common culprit underlying the neurodegenerative process induced by corticosterone and beta-amyloid. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4961787
AbstractMajor depression and Alzheimer’s disease (AD) are highly prevalent psychiatric disorders. Further investigation demonstrated that depression itself is a risk factor for AD, and several associated genetic mutations have been found Moreover, significant proportion of AD patients suffer also suffer from depression. These findings generated interests in finding the neurobiological linkages between depression and AD. The elucidation of pathophysiological mechanisms common in both disorders would be important, as the knowledge could provide additional insights regarding the pathogeneses of the disorders and possible interventions. The present study proposes that synaptic degeneration plays a central role in the pathogenesis of depression and AD. Using in vitro disease models, this study demonstrated abnormalities in pre-synaptic and cytoskeletal proteins, which leads to impaired synaptic function. Further investigation into the upstream events demonstrated the involvement of ubiquitin-mediated protein degradation mechanism and the preferential activation of the autophagic-lysosomal pathway. This study also investigated the neuroprotective properties of the antidepressants imipramine and escitalopram. Antidepressants have originally been thought to exert their therapeutic effects through monoaminergic system modulation. Interestingly, results in this study showed that these two agents were able to ameliorate the observed synaptic protein changes, thereby implicating other possible mechanism of action for antidepressants. In conclusion, this study provides evidence that similar synaptic pathologies exist between depression and AD, which could be responsible for the development of these two disorders. Furthermore, antidepressants may be exerting its effects through alleviating synaptic degeneration.
DegreeDoctor of Philosophy
SubjectCorticosterone.
Amyloid beta-protein.
Synapses.
Nervous system - Degeneration.
Dept/ProgramPsychiatry
Persistent Identifierhttp://hdl.handle.net/10722/180967

 

DC FieldValueLanguage
dc.contributor.advisorLaw, ACK-
dc.contributor.advisorChang, RCC-
dc.contributor.authorWuwongse, Suthicha.-
dc.date.accessioned2013-02-07T06:21:41Z-
dc.date.available2013-02-07T06:21:41Z-
dc.date.issued2012-
dc.identifier.citationWuwongse, S.. (2012). Investigation of synaptic degeneration as a common culprit underlying the neurodegenerative process induced by corticosterone and beta-amyloid. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4961787-
dc.identifier.urihttp://hdl.handle.net/10722/180967-
dc.description.abstractMajor depression and Alzheimer’s disease (AD) are highly prevalent psychiatric disorders. Further investigation demonstrated that depression itself is a risk factor for AD, and several associated genetic mutations have been found Moreover, significant proportion of AD patients suffer also suffer from depression. These findings generated interests in finding the neurobiological linkages between depression and AD. The elucidation of pathophysiological mechanisms common in both disorders would be important, as the knowledge could provide additional insights regarding the pathogeneses of the disorders and possible interventions. The present study proposes that synaptic degeneration plays a central role in the pathogenesis of depression and AD. Using in vitro disease models, this study demonstrated abnormalities in pre-synaptic and cytoskeletal proteins, which leads to impaired synaptic function. Further investigation into the upstream events demonstrated the involvement of ubiquitin-mediated protein degradation mechanism and the preferential activation of the autophagic-lysosomal pathway. This study also investigated the neuroprotective properties of the antidepressants imipramine and escitalopram. Antidepressants have originally been thought to exert their therapeutic effects through monoaminergic system modulation. Interestingly, results in this study showed that these two agents were able to ameliorate the observed synaptic protein changes, thereby implicating other possible mechanism of action for antidepressants. In conclusion, this study provides evidence that similar synaptic pathologies exist between depression and AD, which could be responsible for the development of these two disorders. Furthermore, antidepressants may be exerting its effects through alleviating synaptic degeneration.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.source.urihttp://hub.hku.hk/bib/B49617874-
dc.subject.lcshCorticosterone.-
dc.subject.lcshAmyloid beta-protein.-
dc.subject.lcshSynapses.-
dc.subject.lcshNervous system - Degeneration.-
dc.titleInvestigation of synaptic degeneration as a common culprit underlying the neurodegenerative process induced by corticosterone and beta-amyloid-
dc.typePG_Thesis-
dc.identifier.hkulb4961787-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplinePsychiatry-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b4961787-
dc.date.hkucongregation2013-

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