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. 2009 Feb 2;75(5):1021–1030. doi: 10.1124/mol.108.052357

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Copyright © 2009, The American Society for Pharmacology and Experimental Therapeutics

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Fig. 5. — Inositol depletion mediates the effects of lithium on synapse formation. A, the phosphoinositide cascade. B, bar graph summarizes the effects of GSK-3β inhibitor L803-mts and exogenous myo-inositol on changes in PSD95-GFP puncta (PSDs) after 4-h treatment under control (□) or stimulated (5 mM Li⁺, ▪) conditions. Pretreatment with 1 mM myo-inositol prevented the formation of new PSDs. C, bar graph summarizes the effects of pharmacological modulation of the PtdIns cascade on synapse formation in the absence (□) or presence of 5 mM lithium (▪). Wortmannin [10 μM; wort (10 μM)] but not 100 nM wortmannin [wort(0.1 μM)] induced new synapse formation. Inhibition of PLC with 1 μM U73122 or inhibition of PKC with either 100 nM Gö6976 or 100 nM Ro-31-8220 did not affect the number of PSD95-GFP puncta. D, bar graph summarizes the effects on exogenous PtdIns(4)P on the number of PSD95-GFP puncta under control conditions (□) and during treatment with 5 mM lithium (▪) or 10 μM wortmannin (). PtdIns(4)P was delivered via the shuttle PIP system as described under Materials and Methods. E, bar graph summarizes the effects of 10 μM XE991 on the number of PSD95-GFP puncta under control conditions (). Data are mean ± S.E.M. ^*, p < 0.05, ^**, p < 0.01 relative to untreated control; #, p < 0.01 relative to lithium-induced response in the absence of other treatments (untreated); †, p < 0.01 relative to wortmannin-induced response in the absence of other treatments (untreated); ANOVA with Bonferroni post test.

Inline graphic — Inositol depletion mediates the effects of lithium on synapse formation. A, the phosphoinositide cascade. B, bar graph summarizes the effects of GSK-3β inhibitor L803-mts and exogenous myo-inositol on changes in PSD95-GFP puncta (PSDs) after 4-h treatment under control (□) or stimulated (5 mM Li⁺, ▪) conditions. Pretreatment with 1 mM myo-inositol prevented the formation of new PSDs. C, bar graph summarizes the effects of pharmacological modulation of the PtdIns cascade on synapse formation in the absence (□) or presence of 5 mM lithium (▪). Wortmannin [10 μM; wort (10 μM)] but not 100 nM wortmannin [wort(0.1 μM)] induced new synapse formation. Inhibition of PLC with 1 μM U73122 or inhibition of PKC with either 100 nM Gö6976 or 100 nM Ro-31-8220 did not affect the number of PSD95-GFP puncta. D, bar graph summarizes the effects on exogenous PtdIns(4)P on the number of PSD95-GFP puncta under control conditions (□) and during treatment with 5 mM lithium (▪) or 10 μM wortmannin (). PtdIns(4)P was delivered via the shuttle PIP system as described under Materials and Methods. E, bar graph summarizes the effects of 10 μM XE991 on the number of PSD95-GFP puncta under control conditions (). Data are mean ± S.E.M. ^*, p < 0.05, ^**, p < 0.01 relative to untreated control; #, p < 0.01 relative to lithium-induced response in the absence of other treatments (untreated); †, p < 0.01 relative to wortmannin-induced response in the absence of other treatments (untreated); ANOVA with Bonferroni post test.