Lithium,Inositol and Mitochondria |
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| Authors: | Lilach Toker Galila Agam |
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| Affiliation: | †Department of Psychiatry, University of British Columbia, Vancouver, BC V6T 1Z4, Canada;‡Department of Clinical Biochemistry and Pharmacology and Psychiatry Research Unit, Faculty of Health Sciences, Ben-GurionUniversity of the Negev and Mental Health Center, Beer-Sheva 84170, Israel |
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| Abstract: | Our recent DNA-microarray and proteomicsstudies searching for pathways affected both by chronic lithium treatmentand 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-relatedproteins in the frontal cortex. Differently from previously reportedobservations of aberrant mitochondrial function in bipolar patientswhich leave a causality relationship between mitochondrial dysfunctionand bipolar disorder an open question, the behavioral results of ourrecent report following rotenone treatment tempt us to speculate thatmitochondrial dysfunction predisposes manic behavior and that drugstargeted to ameliorate mitochondrial function are potential preventersof bursting manic episodes. However, the promiscuity of the involvementof mitochondrial dysfunction and impaired autophagy in the pathophysiologyof psychiatric and neurodegenerative disorders raises questions regardingthe credibility and relevance of these findings. |
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| Keywords: | Lithium inositol knockout mice genomics and proteomics mitochondira autophagy |
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