| First Author | Shaldubina A | Year | 2006 |
| Journal | Mol Genet Metab | Volume | 88 |
| Issue | 4 | Pages | 384-8 |
| PubMed ID | 16644257 | Mgi Jnum | J:111651 |
| Mgi Id | MGI:3654617 | Doi | 10.1016/j.ymgme.2006.03.007 |
| Citation | Shaldubina A, et al. (2006) SMIT1 haploinsufficiency causes brain inositol deficiency without affecting lithium-sensitive behavior. Mol Genet Metab 88(4):384-8 |
| abstractText | Two leading hypotheses to explain lithium action in bipolar disorder propose either inositol depletion or inhibition of GSK-3 as mechanisms of action. Behavioral effects of lithium are mimicked in Gsk-3beta(+/-) mice, but the contribution of inositol depletion to these behaviors has not been tested. According to the inositol depletion hypothesis, lithium-sensitive behavior is secondary to impaired phosphatidylinositol synthesis caused by inositol deficiency. By disrupting the sodium myo-inositol transporter1 gene, SMIT1, we show that depletion of brain myo-inositol in SMIT1(+/-) mice has no effect on lithium-sensitive behavior. These findings, taken together with our previous work showing that SMIT(-/-) mice have an even greater depletion of inositol in brain with no reduction in phosphatidylinositol levels, are difficult to reconcile with the current formulation of the inositol depletion hypothesis. |
