- 學位論文
Investigation of synaptic degeneration as a common culprit underlying the neurodegenerative process induced by corticosterone and beta-amyloid
Investigation of synaptic degeneration as a common culprit underlying the neurodegenerative process induced by corticosterone and beta-amyloid
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並列摘要
Major 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.