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Epilepsy, Headache, Vertigo

開催日 2014/9/11
時間 16:00 - 17:00
会場 Poster / Exhibition(Event Hall B)

Growth hormone modulates Arc signaling correlated with behavioral response

  • P1-346
  • Paitoon Srimontri:1 Haruna Hirota:1 Yoshio Hirabayashi:2 Keiko Kato:1 
  • 1:Kyoto Sangyo University, Kyoto, Japan 2:Brain Science Institute, RIKEN, Saitama, Japan 

Growth hormone (GH) has been implicated in a variety of brain functions, including neural development, cognition, and neuroprotection. Previously, we have presented that amygdala-kindling model mouse, an animal model of human temporal lobe epilepsy (TLE), markedly increased both mRNA and protein levels of GH in the brain. Furthermore, infusion of GH into the hippocampus reduced the threshold for afterdischarges generated by the kindling stimulations, which could enhance the progression of seizures. Though the hippocampus and amygdala that receive effects by medial TLE are also key regions in emotion and memory, the involvement of GH expression in emotional behavior remains unclear. Presently, we determined whether infusion of GH could directly induce the expression of these epilepsy-responsive immediate early genes (IEGs), and evaluated whether these IEGs were correlated with anxiety-like behaviors that are often comorbidity with epilepsy. The infusions induced differential expression of Arc, Nr4a1, and Npas4 mRNAs among the IEGs. The infusions also elicited differential behavioral responses, such as varied levels of spontaneous locomotion, self-grooming, and frequency of access to the corner fields in the open-field test, and frequency of open arm entry in the plus maze. Polynomial regression analyses and canonical discriminant analyses between gene expression and behavioral changes demonstrated that the expression level of Arc mRNA was strongly correlated with locomotor activity level (r = 0.71 and 0.92 on days 8 and 10, respectively) and that the correlation was completely discriminable between drugs (error rate = 0 %). Immunofluorescence showed that double-labeled cells expressing GH receptor (GHR) and Arc increased in the side that was ipsilateral to GH infusion, compared to infusions of antagonist and vehicle. This strengthens the idea that GH-GHR signaling induces Arc expression. Taken together, these suggest that the GH-GHR complex modulates Arc signaling, which affects spontaneous locomotor and exploratory behaviors.

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