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postgraduate thesis: Evaluating appropriateness for the use of 6-hydroxydopamine as an experimental model for Parkinson's disease to investigate involvement of tau protein in cognitive dysfunctions of Parkinson's disease

TitleEvaluating appropriateness for the use of 6-hydroxydopamine as an experimental model for Parkinson's disease to investigate involvement of tau protein in cognitive dysfunctions of Parkinson's disease
Authors
Issue Date2015
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Leung, Y. [梁欣]. (2015). Evaluating appropriateness for the use of 6-hydroxydopamine as an experimental model for Parkinson's disease to investigate involvement of tau protein in cognitive dysfunctions of Parkinson's disease. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5435633
AbstractParkinson’s disease (PD) is a debilitating neurodegenerative disorder which progresses from initial motor impairments to development of cognitive dysfunctions and dementia in advanced stages of the disease. Pathological hallmarks of PD include selective loss of dopaminergic neurons in the nigrostriatal pathway and the development of Lewy body inclusions. The pathological events leading to the cognitive dysfunctions appear to be different from those related to motor deficits of PD, but the exact mechanisms are not clear. Studies on postmortem brain samples of PD patients have shown marked axonal pathology and tau pathology in neocortex and hippocampus associated with cognitive dysfunctions. Tau is a microtubule associated protein which, in its non-phosphorylated form, binds to and stabilizes microtubules. Under pathological conditions, tau is hyperphosphorylated and form self-aggregates. However, to study tau pathology in the context of cognitive dysfunctions of PD, a suitable in vivo model is required. Currently, there is no specific in vivo model to mimic the cognitive dysfunctions of PD. Therefore, I evaluated the suitability of a classical toxin model of PD, the 6-hydroxydopamine (6-OHDA) lesion in rats, for the study of tau pathology in cognitive dysfunctions of PD. Sprague Dawley rats underwent stereotaxic lesion surgery for 6-OHDA injection into the medial forebrain bundle (MFB). Motor deficit, memory function, tau expression and phosphorylation were evaluated at 3 weeks post-lesion. Results showed that 6-OHDA lesion was correlated with memory impairment and increased total tau levels in hippocampus, but without increased levels of Ser396 or Ser404 phosphorylated tau. On the other hand, increased levels of Ser396 and Ser404 phosphorylated tau was found in frontal cortex. There was no increase in activation of JNK, which indicated apoptotic neuron degeneration was not increased in these regions. In conclusion, the 6-OHDA lesion in MFB successfully mimicked the tau pathology in cortical regions in the brain, but not in the hippocampus. This study showed that the classical 6-OHDA lesion model of PD could be suitably applied for the study of tau pathology in cognitive dysfunctions of PD.
DegreeMaster of Philosophy
SubjectParkinson's disease - Pathophysiology
Dept/ProgramAnatomy
Persistent Identifierhttp://hdl.handle.net/10722/222912

 

DC FieldValueLanguage
dc.contributor.authorLeung, Yen-
dc.contributor.author梁欣-
dc.date.accessioned2016-02-12T23:12:53Z-
dc.date.available2016-02-12T23:12:53Z-
dc.date.issued2015-
dc.identifier.citationLeung, Y. [梁欣]. (2015). Evaluating appropriateness for the use of 6-hydroxydopamine as an experimental model for Parkinson's disease to investigate involvement of tau protein in cognitive dysfunctions of Parkinson's disease. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5435633-
dc.identifier.urihttp://hdl.handle.net/10722/222912-
dc.description.abstractParkinson’s disease (PD) is a debilitating neurodegenerative disorder which progresses from initial motor impairments to development of cognitive dysfunctions and dementia in advanced stages of the disease. Pathological hallmarks of PD include selective loss of dopaminergic neurons in the nigrostriatal pathway and the development of Lewy body inclusions. The pathological events leading to the cognitive dysfunctions appear to be different from those related to motor deficits of PD, but the exact mechanisms are not clear. Studies on postmortem brain samples of PD patients have shown marked axonal pathology and tau pathology in neocortex and hippocampus associated with cognitive dysfunctions. Tau is a microtubule associated protein which, in its non-phosphorylated form, binds to and stabilizes microtubules. Under pathological conditions, tau is hyperphosphorylated and form self-aggregates. However, to study tau pathology in the context of cognitive dysfunctions of PD, a suitable in vivo model is required. Currently, there is no specific in vivo model to mimic the cognitive dysfunctions of PD. Therefore, I evaluated the suitability of a classical toxin model of PD, the 6-hydroxydopamine (6-OHDA) lesion in rats, for the study of tau pathology in cognitive dysfunctions of PD. Sprague Dawley rats underwent stereotaxic lesion surgery for 6-OHDA injection into the medial forebrain bundle (MFB). Motor deficit, memory function, tau expression and phosphorylation were evaluated at 3 weeks post-lesion. Results showed that 6-OHDA lesion was correlated with memory impairment and increased total tau levels in hippocampus, but without increased levels of Ser396 or Ser404 phosphorylated tau. On the other hand, increased levels of Ser396 and Ser404 phosphorylated tau was found in frontal cortex. There was no increase in activation of JNK, which indicated apoptotic neuron degeneration was not increased in these regions. In conclusion, the 6-OHDA lesion in MFB successfully mimicked the tau pathology in cortical regions in the brain, but not in the hippocampus. This study showed that the classical 6-OHDA lesion model of PD could be suitably applied for the study of tau pathology in cognitive dysfunctions of PD.-
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.subject.lcshParkinson's disease - Pathophysiology-
dc.titleEvaluating appropriateness for the use of 6-hydroxydopamine as an experimental model for Parkinson's disease to investigate involvement of tau protein in cognitive dysfunctions of Parkinson's disease-
dc.typePG_Thesis-
dc.identifier.hkulb5435633-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelMaster-
dc.description.thesisdisciplineAnatomy-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5435633-

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