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Conference Paper: The involvement of synaptic degeneration in major depressive disorder and antidepressant mechanism of action

TitleThe involvement of synaptic degeneration in major depressive disorder and antidepressant mechanism of action
Authors
KeywordsDespression
Corticosterone
Antidepressant
Issue Date2010
PublisherThe Society for Neuroscience.
Citation
The 40th Annual Meeting of the Society for Neuroscience (SfN 2010), San Diego, CA., 13-17 November 2010. How to Cite?
AbstractMajor Depressive Disorder (MDD) is a neuropsychiatric syndrome where patients exhibit symptoms of low mood, anhedonia, and cognitive impairment. Studies have shown an intimate relationship between the effects of stress and the pathophysiology of depression. Elevated cortisol levels resulting from disturbance of the hypothalamus-pituitary-adrenal axis has been observed in depressed patients. Studies have also shown that the hippocampus is severely affected in depression. Although studies have provided evidence on the pathophysiology of depression, the precise mechanisms remain to be elucidated. Increasing lines of evidence have demonstrated synaptic changes in mood disorders, including depression. We hypothesize that progressive synaptic degeneration may initiate pathological changes in healthy neurons and antidepressants can function as a neuroprotective agent. In the present study, we used primary cultures of hippocampal neurons as an experimental model and neurons exposed to corticosterone as an in vitro model for depression. To simulate depression, we used a sub-lethal dosage of corticosterone over a long time point of 48 hours. Immunocytochemical analysis of synaptic and cytoskeletal proteins were used to investigate effects of cortisosterone. Results showed aggregations of the presynaptic proteins, synaptotagmin, and synaptophysin. Microtubule associated protein 2 (MAP2) staining of the dendrites revealed dendritic varicosities. Increased staining of phosphorylated neurofilaments (SMI-312) was also observed. Pre-treatment with imipramine and escitalopram (20 μM for both) were able to alleviate the detrimental effects. These results suggest the involvement of synaptic degeneration in corticosterone-induced toxicity and the ability of antidepressants to alleviate the observed pathology. Hence, synaptic degeneration could contribute to the pathophysiology of depression and antidepressants could be exerting its effects through synapse protection. Further studies to elucidate the synapse-related neuroprotective mechanisms of antidepressants are planned.
DescriptionPoster session 162 - Anxiety Disorders: Experimental Therapeutics
Ref. no. 162.1/V9
Persistent Identifierhttp://hdl.handle.net/10722/142624

 

DC FieldValueLanguage
dc.contributor.authorWuwongse, Sen_US
dc.contributor.authorHung, HLen_US
dc.contributor.authorChang, RCCen_US
dc.contributor.authorLaw, ACKen_US
dc.date.accessioned2011-10-28T02:53:24Z-
dc.date.available2011-10-28T02:53:24Z-
dc.date.issued2010en_US
dc.identifier.citationThe 40th Annual Meeting of the Society for Neuroscience (SfN 2010), San Diego, CA., 13-17 November 2010.en_US
dc.identifier.urihttp://hdl.handle.net/10722/142624-
dc.descriptionPoster session 162 - Anxiety Disorders: Experimental Therapeutics-
dc.descriptionRef. no. 162.1/V9-
dc.description.abstractMajor Depressive Disorder (MDD) is a neuropsychiatric syndrome where patients exhibit symptoms of low mood, anhedonia, and cognitive impairment. Studies have shown an intimate relationship between the effects of stress and the pathophysiology of depression. Elevated cortisol levels resulting from disturbance of the hypothalamus-pituitary-adrenal axis has been observed in depressed patients. Studies have also shown that the hippocampus is severely affected in depression. Although studies have provided evidence on the pathophysiology of depression, the precise mechanisms remain to be elucidated. Increasing lines of evidence have demonstrated synaptic changes in mood disorders, including depression. We hypothesize that progressive synaptic degeneration may initiate pathological changes in healthy neurons and antidepressants can function as a neuroprotective agent. In the present study, we used primary cultures of hippocampal neurons as an experimental model and neurons exposed to corticosterone as an in vitro model for depression. To simulate depression, we used a sub-lethal dosage of corticosterone over a long time point of 48 hours. Immunocytochemical analysis of synaptic and cytoskeletal proteins were used to investigate effects of cortisosterone. Results showed aggregations of the presynaptic proteins, synaptotagmin, and synaptophysin. Microtubule associated protein 2 (MAP2) staining of the dendrites revealed dendritic varicosities. Increased staining of phosphorylated neurofilaments (SMI-312) was also observed. Pre-treatment with imipramine and escitalopram (20 μM for both) were able to alleviate the detrimental effects. These results suggest the involvement of synaptic degeneration in corticosterone-induced toxicity and the ability of antidepressants to alleviate the observed pathology. Hence, synaptic degeneration could contribute to the pathophysiology of depression and antidepressants could be exerting its effects through synapse protection. Further studies to elucidate the synapse-related neuroprotective mechanisms of antidepressants are planned.-
dc.languageengen_US
dc.publisherThe Society for Neuroscience.-
dc.relation.ispartofAnnual Meeting of the Society for Neuroscience, SfN 2010en_US
dc.subjectDespression-
dc.subjectCorticosterone-
dc.subjectAntidepressant-
dc.titleThe involvement of synaptic degeneration in major depressive disorder and antidepressant mechanism of actionen_US
dc.typeConference_Paperen_US
dc.identifier.emailWuwongse, S: suthicha@hku.hken_US
dc.identifier.emailHung, HL: chlhung@hku.hken_US
dc.identifier.emailChang, RCC: rccchang@hkucc.hku.hk-
dc.identifier.emailLaw, ACK: acklaw@hku.hk-
dc.identifier.authorityChang, RCC=rp00470en_US
dc.identifier.authorityLaw, ACK=rp00262en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros184451en_US
dc.publisher.placeUnited States-
dc.customcontrol.immutablesml 130715-

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