title: Lithium, inositol and mitochondria.
abstract: Our recent DNA-microarray and proteomics studies searching for pathways affected both by chronic lithium treatment and by knockout of each of two genes (IMPA1 or Slc5a3) encoding for proteins related to inositol metabolism, indicated up-regulation of mitochondria-related genes and autophagy-related proteins in the frontal cortex. Differently from previously reported observations of aberrant mitochondrial function in bipolar patients which leave a causality relationship between mitochondrial dysfunction and bipolar disorder an open question, the behavioral results of our recent report following rotenone treatment tempt us to speculate that mitochondrial dysfunction predisposes manic behavior and that drugs targeted to ameliorate mitochondrial function are potential preventers of bursting manic episodes. However, the promiscuity of the involvement of mitochondrial dysfunction and impaired autophagy in the pathophysiology of psychiatric and neurodegenerative disorders raises questions regarding the credibility and relevance of these findings.
authors.affiliation: †Department of Psychiatry, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Lilach
authors.initials: L
authors.lastname: Toker
authors.affiliation: ‡Department of Clinical Biochemistry and Pharmacology and Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev and Mental Health Center, Beer-Sheva 84170, Israel.
authors.forename: Galila
authors.initials: G
authors.lastname: Agam
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007294:Inositol / Q000378:metabolism*; D018020:Lithium Compounds / Q000494:pharmacology*; D001523:Mental Disorders / Q000188:drug therapy / Q000503:physiopathology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds; D007294:Inositol
keywords: Lithium; autophagy; genomics and proteomics; inositol; knockout mice; mitochondira