Association of Myoinositol Transporters with Schizophrenia and Bipolar Disorder: Evidence from Human and Animal Studies

Evidence from animal and human studies has linkedmyo-inositol (MI) with the pathophysiology and/or treatment of psychiatric disorders such as schizophrenia and bipolar disorder. However, there is still controversy surrounding the definitive role of MI in these disorders. Given that brain MI is differentially regulated by three transporters – SMIT1, SMIT2 and/or HMIT (encoded by the genes:SLC5A3, SLC5A11,andSLC2A13, respectively) – we used available datasets to describe the distribution in mouse and human brain of the different MI transporters and to examine changes in mRNA expression of these transporters in patients with schizophrenia and bipolar disorder. We found a differential distribution of the mRNA of each of the t hree MI transporters in both human and mouse brain regions. Interestingly, while individual neurons express SMIT1 and HMIT, non-neuronal cells express SMIT2, thus partially accounting for different uptake levels of MI and concordance to downstream second messenger signaling pathways. We also found t hat the expression of MI transporters is significantly changed in schizophrenia and bipolar disorder in a diagnostic-, brain region- and subtype-specific manner. We then examined the effects of germline deletion in mice ofSlc5a3 on behavioral phenotypes related to schizophrenia and bipolar disorder. This gene deletion produces behavioral deficits that mirror some specific symptoms of schizophrenia and bipolar disorder. Finally, chronic administration of MI wa...
Source: Molecular Neuropsychiatry - Category: Neuroscience Source Type: research