title: Effects of Mood Stabilizers on Brain Energy Metabolism in Mice Submitted to an Animal Model of Mania Induced by Paradoxical Sleep Deprivation.
abstract: There is a body of evidence suggesting that mitochondrial dysfunction is involved in bipolar disorder (BD) pathogenesis. Studies suggest that abnormalities in circadian cycles are involved in the pathophysiology of affective disorders; paradoxical sleep deprivation (PSD) induces hyperlocomotion in mice. Thus, the present study aims to investigate the effects of lithium (Li) and valproate (VPA) in an animal model of mania induced by PSD for 96 h. PSD increased exploratory activity, and mood stabilizers prevented PSD-induced behavioral effects. PSD also induced a significant decrease in the activity of complex II-III in hippocampus and striatum; complex IV activity was decreased in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex. Additionally, VPA administration was able to prevent PSD-induced inhibition of complex II-III and IV activities in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex, whereas Li administration prevented PSD-induced inhibition only in prefrontal cortex and hippocampus. Regarding the enzymes of Krebs cycle, only citrate synthase activity was increased by PSD in prefrontal cortex. We also found a similar effect in creatine kinase, an important enzyme that acts in the buffering of ATP levels in brain; its activity was increased in prefrontal cortex, hippocampus and cerebral cortex. These results are consistent with the connection of mitochondrial dysfunction and hyperactivity in BD and suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.
authors.affiliation: Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, Criciúma, SC, 88806-000, Brazil, emiliostreck@gmail.com.
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
authors.forename: Giselli
authors.initials: G
authors.lastname: Scaini
authors.forename: Gabriela C
authors.initials: GC
authors.lastname: Jeremias
authors.forename: Gislaine T
authors.initials: GT
authors.lastname: Rezin
authors.forename: Cinara L
authors.initials: CL
authors.lastname: Gonçalves
authors.forename: Gabriela K
authors.initials: GK
authors.lastname: Ferreira
authors.forename: Gislaine Z
authors.initials: GZ
authors.lastname: Réus
authors.forename: Wilson R
authors.initials: WR
authors.lastname: Resende
authors.forename: Samira S
authors.initials: SS
authors.lastname: Valvassori
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
authors.forename: Mônica L
authors.initials: ML
authors.lastname: Andersen
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000339:Affect / Q000187:drug effects*; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000378:metabolism* / Q000523:psychology*; D001923:Brain Chemistry / Q000187:drug effects*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D016651:Lithium Carbonate / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D012892:Sleep Deprivation / Q000378:metabolism* / Q000523:psychology*; D012895:Sleep, REM; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D018692:Antimanic Agents; D016651:Lithium Carbonate; D014635:Valproic Acid; D000255:Adenosine Triphosphate; D002950:Citrate (si)-Synthase