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Lithium ameliorates open-field and elevated plus maze behaviors, and brain phospho-glycogen synthase kinase 3-beta expression in fragile X syndrome model mice.

AbstractOBJECTIVE:
To investigate whether lithium modifies open-field and elevated plus maze behavior, and brain phospho-glycogen synthase kinase 3 (P-GSK3beta) expression in Fmr1 knockout mice.
METHODS:
One hundred and eighty FVB mice, including knockout and wild type, with an age of 30 days were used. An open-field and elevated plus maze was utilized to test behavior, while western blot was used to measure the P-GSK3beta expression. Six groups were formed: control (saline), lithium chloride 30, 60, 90, 120, and 200 mg/kg. The experiments were carried out in the Institute of Neuroscience, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China between January and June 2012.
RESULTS:
Lithium significantly decreased total distance, crossing, central area time, and center entry in the open-field test (p<0.05), and significantly reduced open-arm tracking, open-arm entry, and open-arm time in the elevated plus maze (p<0.05) in knockout mice. In wild type mice, significant changes were observed in both behavior tests in some treatment groups. Lithium ameliorated P-GSK3beta expression in the hippocampus of all the treatment groups in knockout mice (p<0.05). However, lithium did not modify either GSK3beta expression in tissues of knockout mice, or P-GSK3beta or GSK3beta expression in tissues of wild type mice.
CONCLUSION:
Lithium ameliorated open-field and elevated plus maze behaviors of Fmr1 knockout mice. This effect may be related to its enhancement of P-GSK3beta expression. Our findings suggest that lithium might have a therapeutic effect in fragile X syndrome.
AuthorsXi Chen, Weiwen Sun, Ying Pan, Quan Yang, Kaiyi Cao, Jin Zhang, Yizhi Zhang, Mincong Chen, Feidi Chen, Yueling Huang, Lijun Dai, Shengqiang Chen
JournalNeurosciences (Riyadh, Saudi Arabia) (Neurosciences (Riyadh)) Vol. 18 Issue 4 Pg. 356-62 (Oct 2013) ISSN: 1319-6138 [Print] Saudi Arabia
PMID24141459 (Publication Type: Journal Article)
Chemical References
  • Antimanic Agents
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Glycogen Synthase Kinase 3
  • Lithium Chloride
Topics
  • Animals
  • Antimanic Agents (pharmacology)
  • Behavior, Animal (drug effects)
  • Blotting, Western
  • Brain (drug effects, enzymology)
  • Disease Models, Animal
  • Fragile X Syndrome (enzymology)
  • Glycogen Synthase Kinase 3 (biosynthesis)
  • Glycogen Synthase Kinase 3 beta
  • Immunohistochemistry
  • Lithium Chloride (pharmacology)
  • Maze Learning (drug effects)
  • Mice
  • Mice, Knockout

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