A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice

Shiori Ogawa, Chang Hyuk Kwon, Jing Zhou, Della Koovakkattu, Luis F. Parada, Christopher M. Sinton

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Conditional deletion of Pten (phosphatase and tensin homolog on chromosome ten) in differentiated cortical and hippocampal neurons in the mouse results in seizures, macrocephaly, social interaction deficits and anxiety, reminiscent of human autism spectrum disorder. Here we extended our previous examination of these mice using electroencephalogram/electromyogram (EEG/EMG) monitoring and found age-related increases in spontaneous seizures, which were correlated with cellular dispersion in the hippocampal dentate gyrus. Increased spontaneous locomotor activity in the open field on the first and the second day of a 3-day continuous study suggested heightened anxiety in Pten mutant mice. In contrast, the mutants exhibited decreased wheel running activity, which may reflect reduced adaptability to a novel environment. Synchronization to the light-dark cycle was normal, but for up to 28 days under constant darkness, the Pten mutants maintained a significantly lengthened and remarkably constant free-running period of almost exactly 24 h. This result implies the involvement of Pten in the maintenance of circadian rhythms, which we interpret as being due to an effect on the phosphatidylinositol 3-kinase (PI3K) signaling cascade.

Original languageEnglish (US)
Pages (from-to)112-123
Number of pages12
JournalBrain Research
Volume1168
Issue number1
DOIs
StatePublished - Sep 7 2007

Fingerprint

Running
Seizures
Phenotype
Anxiety
Phosphatidylinositol 3-Kinase
Megalencephaly
Parahippocampal Gyrus
Darkness
Dentate Gyrus
Photoperiod
Electromyography
Locomotion
Interpersonal Relations
Circadian Rhythm
Phosphoric Monoester Hydrolases
Electroencephalography
Chromosomes
Maintenance
Neurons
Autism Spectrum Disorder

Keywords

  • Anxiety
  • Autism
  • Circadian rhythm
  • EEG/EMG
  • Epilepsy
  • Tau

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Ogawa, S., Kwon, C. H., Zhou, J., Koovakkattu, D., Parada, L. F., & Sinton, C. M. (2007). A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice. Brain Research, 1168(1), 112-123. https://doi.org/10.1016/j.brainres.2007.06.074

A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice. / Ogawa, Shiori; Kwon, Chang Hyuk; Zhou, Jing; Koovakkattu, Della; Parada, Luis F.; Sinton, Christopher M.

In: Brain Research, Vol. 1168, No. 1, 07.09.2007, p. 112-123.

Research output: Contribution to journalArticle

Ogawa, S, Kwon, CH, Zhou, J, Koovakkattu, D, Parada, LF & Sinton, CM 2007, 'A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice', Brain Research, vol. 1168, no. 1, pp. 112-123. https://doi.org/10.1016/j.brainres.2007.06.074
Ogawa, Shiori ; Kwon, Chang Hyuk ; Zhou, Jing ; Koovakkattu, Della ; Parada, Luis F. ; Sinton, Christopher M. / A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice. In: Brain Research. 2007 ; Vol. 1168, No. 1. pp. 112-123.
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