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Wong G.T.H.,Neurodysfunction Research Laboratory | Wong G.T.H.,Laboratory of Neurodegenerative Diseases | Chang R.C.C.,Laboratory of Neurodegenerative Diseases | Chang R.C.C.,University of Hong Kong | And 2 more authors.
Ageing Research Reviews | Year: 2013

Depression is one of the most common psychiatric disorders with inadequately understood disease mechanisms. It has long been considered that dendritic regression and decrease in the number of dendritic spines are involved in depression. Dendrites made up of microtubules and actin filaments form synapses with neighboring neurons, which come together as an important communication network. Cytoskeletal proteins undergo post-translational modifications to define their structure and function. In depression and other psychiatric disorders, post-translational modifications may be disrupted that can result in altered cytoskeletal functions. The disruption of microtubule and actin in terms of morphology and functions may be a leading cause of dendritic regression and decrease in dendritic spine in depression. © 2012. Source

Wuwongse S.,Neurodysfunction Research Laboratory | Wuwongse S.,Laboratory of Neurodegenerative Diseases | Cheng S.S.Y.,Laboratory of Neurodegenerative Diseases | Wong G.T.H.,Neurodysfunction Research Laboratory | And 9 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2013

The relationship between Alzheimer's disease (AD) and depression has been well established in terms of epidemiological and clinical observations. Depression has been considered to be both a symptom and risk factor of AD. Several genetic and neurobiological mechanisms have been described to underlie these two disorders. Despite the accumulating knowledge on this topic, the precise neuropathological mechanisms remain to be elucidated. In this study, we propose that synaptic degeneration plays an important role in the disease progression of depression and AD. Using primary culture of hippocampal neurons treated with oligomeric Aβ and corticosterone as model agents for AD and depression, respectively, we found significant changes in the pre-synaptic vesicle proteins synaptophysin and synaptotagmin. We further investigated whether the observed protein changes affected synaptic functions. By using FM®4-64 fluorescent probe, we showed that synaptic functions were compromised in treated neurons. Our findings led us to investigate the involvement of protein degradation mechanisms in mediating the observed synaptic protein abnormalities, namely, the ubiquitin-proteasome system and autophagy. We found up-regulation of ubiquitin-mediated protein degradation, and the preferential signaling for the autophagic-lysosomal degradation pathway. Lastly, we investigated the neuroprotective role of different classes of antidepressants. Our findings demonstrated that the antidepressants Imipramine and Escitalopram were able to rescue the observed synaptic protein damage. In conclusion, our study shows that synaptic degeneration is an important common denominator underlying depression and AD, and alleviation of this pathology by antidepressants may be therapeutically beneficial. © 2013 Elsevier B.V. Source

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