title: Glial-specific gene alterations associated with manic behaviors.
abstract: BACKGROUND
  Glial dysfunction has been purported to be important to the pathophysiology of bipolar illness. However, manic behavior has not been previously demonstrated to result as a consequence of glial pathology. The aim of the current study was to assess the behaviors of the glial-specific sodium pump alpha2 subunit (ATP1A2) knockout (KO) heterozygote mice to determine if a glial-specific abnormality can produce manic-like behavior.
  
  
  METHODS
  Activity and behavior of hemideficient sodium pump alpha2 KO mice and wild-type (WT) littermates (C57BL6/Black Swiss background) were examined at baseline, following forced swimming stress and restraint stress and after 3 days of sleep deprivation.
  
  
  CONCLUSIONS
  At baseline, the 24-h total distance traveled and center time were significantly greater in KO mice, but there were no behavioral differences with sweet water preference or with inactivity time during forced swim or tail suspension tests. After restraint stress or forced swimming stress, there were no differences in activity. Three days of sleep deprivation utilizing the inverted flowerpot method induced a significant increase in the distance traveled by the KO versus WT mice in the 30-min observation period (p=0.016). Lithium pretreatment has no effect on WT animals versus their baseline but significantly reduces hyperactivity induced by sleep deprivation in KO. Knockout of the glial-specific alpha2 isoform is associated with some manic behaviors compared to WT littermates, suggesting that glial dysfunction could be associated with mania.
authors.affiliation: Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY, 40202, USA, ylgao001@louisville.edu.
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Gao
authors.forename: Malhar
authors.initials: M
authors.lastname: Jhaveri
authors.forename: Zhenmin
authors.initials: Z
authors.lastname: Lei
authors.forename: Brandy L
authors.initials: BL
authors.lastname: Chaneb
authors.forename: Jerry
authors.initials: J
authors.lastname: Lingrel
authors.forename: Rif S
authors.initials: RS
authors.lastname: El-Mallakh