title: Effects of antidepressant drugs on synaptic protein levels and dendritic outgrowth in hippocampal neuronal cultures.
abstract: The alteration of hippocampal plasticity has been proposed to play a critical role in both the pathophysiology and treatment of depression. In this study, the ability of different classes of antidepressant drugs (escitalopram, fluoxetine, paroxetine, sertraline, imipramine, tranylcypromine, and tianeptine) to mediate the expression of synaptic proteins and dendritic outgrowth in rat hippocampal neurons was investigated under toxic conditions induced by B27 deprivation, which causes hippocampal cell death. Postsynaptic density protein-95 (PSD-95), brain-derived neurotrophic factor (BDNF), and synaptophysin (SYP) levels were evaluated using Western blot analyses. Additionally, dendritic outgrowth was examined to determine whether antidepressant drugs affect the dendritic morphology of hippocampal neurons in B27-deprived cultures. Escitalopram, fluoxetine, paroxetine, sertraline, imipramine, tranylcypromine, and tianeptine significantly prevented B27 deprivation-induced decreases in levels of PSD-95, BDNF, and SYP. Moreover, the independent application of fluoxetine, paroxetine, and sertraline significantly increased levels of BDNF under normal conditions. All antidepressant drugs significantly increased the total outgrowth of hippocampal dendrites under B27 deprivation. Specific inhibitors of calcium/calmodulin kinase II (CaMKII), KN-93, protein kinase A (PKA), H-89, or phosphatidylinositol 3-kinase (PI3K), LY294002, significantly decreased the effects of antidepressant drugs on dendritic outgrowth, whereas this effect was observed only with tianeptine for the PI3K inhibitor. Taken together, these results suggest that certain antidepressant drugs can enhance synaptic protein levels and encourage dendritic outgrowth in hippocampal neurons. Furthermore, effects on dendritic outgrowth likely require CaMKII, PKA, or PI3K signaling pathways. The observed effects may be may be due to chronic treatment with antidepressant drugs.
authors.affiliation: Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Seo
authors.affiliation: Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
authors.forename: Chan Hong
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
authors.forename: Hye Yeon
authors.initials: HY
authors.lastname: Cho
authors.affiliation: Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea; Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Republic of Korea; Department of Health Science and Technology, Graduate School of Inje University, Busan, Republic of Korea.
authors.forename: Jung Goo
authors.initials: JG
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Republic of Korea.
authors.forename: Bong Ju
authors.initials: BJ
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: InAm Neuroscience Research Center, Wonkwang University, Sanbon Hospital, Gunpo, Republic of Korea.
authors.forename: Wongi
authors.initials: W
authors.lastname: Seol
authors.affiliation: Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea; Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Republic of Korea; Department of Health Science and Technology, Graduate School of Inje University, Busan, Republic of Korea. Electronic address: neuro109@hanmail.net.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea; Department of Health Science and Technology, Graduate School of Inje University, Busan, Republic of Korea. Electronic address: swpark@inje.ac.kr.
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D049108:Cell Enlargement / Q000187:drug effects; D002478:Cells, Cultured; D015283:Citalopram / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007099:Imipramine / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D017374:Paroxetine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020280:Sertraline / Q000494:pharmacology; D013841:Thiazepines / Q000494:pharmacology; D014191:Tranylcypromine / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D009419:Nerve Tissue Proteins; D013841:Thiazepines; D005473:Fluoxetine; D015283:Citalopram; C050504:tianeptine; D014191:Tranylcypromine; D017374:Paroxetine; D007099:Imipramine; D020280:Sertraline
keywords: Antidepressant drugs; Dendritic outgrowth; Hippocampal plasticity; Signaling; Synaptic proteins