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Effects of mood‐stabilizing drugs on dendritic outgrowth and synaptic protein levels in primary hippocampal neurons
Author(s) -
Park Sung Woo,
Lee Jung Goo,
Seo Mi Kyoung,
Cho Hye Yeon,
Lee Chan Hong,
Lee Ji Heon,
Lee Bong Ju,
Baek Jun Hyung,
Seol Wongi,
Kim Young Hoon
Publication year - 2015
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1111/bdi.12262
Subject(s) - hippocampal formation , neuroscience , mood , psychology , medicine , clinical psychology
Objectives Mood‐stabilizing drugs, such as lithium (Li) and valproate ( VPA ), are widely used for the treatment of bipolar disorder, a disease marked by recurrent episodes of mania and depression. Growing evidence suggests that Li exerts neurotrophic and neuroprotective effects, leading to an increase in neural plasticity. The present study investigated whether other mood‐stabilizing drugs produce similar effects in primary hippocampal neurons. Methods The effects of the mood‐stabilizing drugs Li, VPA , carbamazepine ( CBZ ), and lamotrigine ( LTG ) on hippocampal dendritic outgrowth were examined. Western blotting analysis was used to measure the expression of synaptic proteins – that is, brain‐derived neurotrophic factor ( BDNF ), postsynaptic density protein‐95 ( PSD ‐95), neuroligin 1 ( NLG 1), β‐neurexin, and synaptophysin ( SYP ). To determine neuroprotective effects, we used a B27‐deprivation cytotoxicity model which causes hippocampal cell death upon removal of B27 from the culture medium. Results Li (0.5–2.0 mM ), VPA (0.5–2.0 mM ), CBZ (0.01–0.10 mM ), and LTG (0.01–0.10 mM ) significantly increased dendritic outgrowth. The neurotrophic effect of Li and VPA was blocked by inhibition of phosphatidylinositol 3‐kinase, extracellular signal‐regulated kinase, and protein kinase A signaling; the effects of CBZ and LTG were not affected by inhibition of these signaling pathways. Li, VPA, and CBZ prevented B27 deprivation‐induced decreases in BDNF, PSD‐95, NLG1, β‐neurexin, and SYP levels, whereas LTG did not. Conclusions These results suggest that Li, VPA , CBZ , and LTG exert neurotrophic effects by promoting dendritic outgrowth; however, the mechanism of action differs. Furthermore, certain mood‐stabilizing drugs may exert neuroprotective effects by enhancing synaptic protein levels against cytotoxicity in hippocampal cultures.