title: Divergent effects of lithium and sodium valproate on brain-derived neurotrophic factor (BDNF) production in human astrocytoma cells at therapeutic concentrations.
abstract: Mood stabilizers such as lithium (Li) or valproic acid (VPA) are used in the therapy of bipolar disorders, but the mechanisms by which these medicines work is unclear. Recently, neuroprotection has attracted attention as a potential action for VPA and Li. The close spatial relationship of the pre- and post-synapse with an astrocyte process within a 'tripartite synapse' suggests that mood stabilizer actions on astrocytes may be important. Therefore, we examined the effect of Li and VPA, at therapeutic concentrations, on brain-derived neurotrophic factor (BDNF) production in cultured human astrocytoma cells over an extended period of exposure. Released (extracellular) and intracellular BDNF was measured with sandwich-ELISA. Intracellular BDNF mRNA was also quantified using RT-PCR. VPA treatment potentiated the level of extracellular BDNF, whereas Li reduced it. Furthermore, VPA caused increased intracellular levels of BDNF protein and mRNA, while exposure to Li led to no significant differences compared to control cells. We suggest the possibility that VPA and Li have divergent effects on astrocyte BDNF production. Mood stabilizers play an essential role in regulating BDNF not only in neurons, but also in astrocytes. These findings could form the basis of a new astrocyte-targeted approach towards developing effective medications to treat bipolar disorders.
authors.affiliation: Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishino
authors.forename: Koji
authors.initials: K
authors.lastname: Ohtomo
authors.forename: Yukio
authors.initials: Y
authors.lastname: Numata
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Sato
authors.forename: Norimichi
authors.initials: N
authors.lastname: Nakahata
authors.forename: Masatake
authors.initials: M
authors.lastname: Kurita
mesh_terms: D001253:Astrocytes / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002452:Cell Count / Q000706:statistics & numerical data; D045744:Cell Line, Tumor; D006801:Humans; D018021:Lithium Chloride / Q000009:adverse effects / Q000494:pharmacology*; D014635:Valproic Acid / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D014635:Valproic Acid; D018021:Lithium Chloride