PMID- 25307211
OWN - NLM
STAT- MEDLINE
DCOM- 20160421
LR  - 20181202
IS  - 1399-5618 (Electronic)
IS  - 1398-5647 (Linking)
VI  - 17
IP  - 3
DP  - 2015 May
TI  - Effects of mood-stabilizing drugs on dendritic outgrowth and synaptic protein 
      levels in primary hippocampal neurons.
PG  - 278-90
LID - 10.1111/bdi.12262 [doi]
AB  - 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 (NLG1), beta-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, beta-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.
CI  - (c) 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Park, Sung Woo
AU  - Park SW
AD  - Paik Institute for Clinical Research, Inje University, Busan, Korea; Department 
      of Health Science and Technology, Graduate School of Inje University, Busan, 
      Korea.
FAU - Lee, Jung Goo
AU  - Lee JG
FAU - Seo, Mi Kyoung
AU  - Seo MK
FAU - Cho, Hye Yeon
AU  - Cho HY
FAU - Lee, Chan Hong
AU  - Lee CH
FAU - Lee, Ji Heon
AU  - Lee JH
FAU - Lee, Bong Ju
AU  - Lee BJ
FAU - Baek, Jun Hyung
AU  - Baek JH
FAU - Seol, Wongi
AU  - Seol W
FAU - Kim, Young Hoon
AU  - Kim YH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141013
PL  - Denmark
TA  - Bipolar Disord
JT  - Bipolar disorders
JID - 100883596
RN  - 0 (Antimanic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cell Adhesion Molecules, Neuronal)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, rat)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lithium Compounds)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Synaptophysin)
RN  - 0 (Syp protein, rat)
RN  - 0 (Triazines)
RN  - 0 (neuroligin 1)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - U3H27498KS (Lamotrigine)
SB  - IM
MH  - Animals
MH  - Antimanic Agents/*pharmacology
MH  - *Bipolar Disorder
MH  - Brain-Derived Neurotrophic Factor/drug effects/metabolism
MH  - Cell Adhesion Molecules, Neuronal/drug effects/metabolism
MH  - Dendrites/*drug effects
MH  - Disks Large Homolog 4 Protein
MH  - Hippocampus/cytology
MH  - Intracellular Signaling Peptides and Proteins/drug effects/metabolism
MH  - Lamotrigine
MH  - Lithium Compounds/*pharmacology
MH  - Membrane Proteins/drug effects/metabolism
MH  - Neurons/*drug effects
MH  - Neuroprotective Agents
MH  - Phosphatidylinositol 3-Kinases
MH  - Rats
MH  - Synaptophysin/drug effects/metabolism
MH  - Triazines/*pharmacology
MH  - Valproic Acid/*pharmacology
OTO - NOTNLM
OT  - dendritic outgrowth
OT  - mood-stabilizing drugs
OT  - neural plasticity
OT  - signaling
OT  - synaptic proteins
EDAT- 2014/10/14 06:00
MHDA- 2016/04/22 06:00
CRDT- 2014/10/14 06:00
PHST- 2014/03/12 00:00 [received]
PHST- 2014/07/23 00:00 [accepted]
PHST- 2014/10/14 06:00 [entrez]
PHST- 2014/10/14 06:00 [pubmed]
PHST- 2016/04/22 06:00 [medline]
AID - 10.1111/bdi.12262 [doi]
PST - ppublish
SO  - Bipolar Disord. 2015 May;17(3):278-90. doi: 10.1111/bdi.12262. Epub 2014 Oct 13.