Abstract
BackgroundMitochondrial short and long-range movements are necessary to generate the energy needed for synaptic signaling and plasticity. Therefore, an effective mechanism to transport and anchor mitochondria to pre- and post-synaptic terminals is as important as functional mitochondria in neuronal firing. Mitochondrial movement range is regulated by phosphorylation of cytoskeletal and motor proteins in addition to changes in mitochondrial membrane potential. Movement direction is regulated by serotonin and dopamine levels. However, data on mitochondrial movement defects and their involvement in defective signaling and neuroplasticity in relationship with mood disorders is scarce. We have previously reported the effects of lithium, valproate and a new antipsychotic, paliperidone on protein expression levels at the synaptic level.HypothesisMitochondrial function defects have recently been implicated in schizophrenia and bipolar disorder. We postulate that mood stabilizer treatment has a profound effect on mitochondrial function, synaptic plasticity, mitochondrial migration and direction of movement.MethodsSynaptoneurosomal preparations from rat pre-frontal cortex were obtained after 28 daily intraperitoneal injections of lithium, valproate and paliperidone. Phosphorylated proteins were identified using 2D-DIGE and nano LC-ESI tandem mass spectrometry.ResultsLithium, valproate and paliperidone had a substantial and common effect on the phosphorylation state of specific actin, tubulin and myosin isoforms as well as other proteins associated with neurofilaments. Furthermore, different subunits from complex III and V of the electron transfer chain were heavily phosphorylated by treatment with these drugs indicating selective phosphorylation.ConclusionsMood stabilizers have an effect on mitochondrial function, mitochondrial movement and the direction of this movement. The implications of these findings will contribute to novel insights regarding clinical treatment and the mode of action of these drugs.
Highlights
Mood stabilizers have an effect on mitochondrial function, mitochondrial movement and the direction of this movement
Mitochondrial dysfunction appears to have a strong impact on the pathogenesis of bipolar disorder (BD) and schizophrenia little is known about the effects of impaired mitochondrial movement [1]
2D-DIGE protein phosphorylation Staining with ProQ Diamond indicated that specific cytoskeletal, mitochondrial, and regulatory proteins were highly phosphorylated ($7 fold) in response to paliperidone, lithium, and valproate chronic treatment
Summary
Mitochondrial dysfunction appears to have a strong impact on the pathogenesis of bipolar disorder (BD) and schizophrenia little is known about the effects of impaired mitochondrial movement [1]. Mitochondrial short and long-range movement is necessary to generate the energy needed for synaptic signaling and plasticity [2] This energy is supplied in the form of Adenosine 59-triphosphate (ATP) by a series of chemical reactions that take place within the electron transport chain (ETC). Drugs that uncouple the proton gradient across the mitochondrial inner membrane and that inhibit ATPA will regulate mitochondrial movement. Mitochondrial short and long-range movements are necessary to generate the energy needed for synaptic signaling and plasticity. Mitochondrial movement range is regulated by phosphorylation of cytoskeletal and motor proteins in addition to changes in mitochondrial membrane potential. We have previously reported the effects of lithium, valproate and a new antipsychotic, paliperidone on protein expression levels at the synaptic level
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
