Lithium treatment alleviates impaired cognition in a mouse model of fragile X syndrome

M. K. King, R. S. Jope

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Fragile X syndrome (FXS) is caused by suppressed expression of fragile X mental retardation protein (FMRP), which results in intellectual disability accompanied by many variably manifested characteristics, such as hyperactivity, seizures and autistic-like behaviors. Treatment of mice that lack FMRP, Fmr1 knockout (KO) mice, with lithium has been reported to ameliorate locomotor hyperactivity, prevent hypersensitivity to audiogenic seizures, improve passive avoidance behavior and attenuate sociability deficits. To focus on the defining characteristic of FXS, which is cognitive impairment, we tested if lithium treatment ameliorated impairments in four cognitive tasks in Fmr1 KO mice, tested if the response to lithium differed in adolescent and adult mice and tested if therapeutic effects persisted after discontinuation of lithium administration. Fmr1 KO mice displayed impaired cognition in the novel object detection task, temporal ordering for objects task and coordinate and categorical spatial processing tasks. Chronic lithium treatment of adolescent (from 4 to 8weeks of age) and adult (from 8 to 12weeks of age) mice abolished cognitive impairments in all four cognitive tasks. Cognitive deficits returned after lithium treatment was discontinued for 4weeks. These results show that Fmr1 KO mice exhibit severe impairments in these cognitive tasks, that lithium is equally effective in normalizing cognition in these tasks whether it is administered to young or adult mice and that lithium administration must be continued for the cognitive improvements to be sustained. These findings provide further evidence that lithium administration may be beneficial for individuals with FXS. Chronic lithium treatment of adult or adolescent FX mice reverses impaired novel object detection performance.

Original languageEnglish (US)
Pages (from-to)723-731
Number of pages9
JournalGenes, Brain and Behavior
Volume12
Issue number7
DOIs
StatePublished - Oct 2013

Keywords

  • Cognition
  • Fragile X syndrome
  • Learning
  • Lithium
  • Novel object detection
  • Spatial processing

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology

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