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

Evaluating the therapeutic potential of lithium on the alleviation of neuromarphological and behavioral deficits in AKT-promoted P19 embryonal carcinoma cells and Akt1 mouse model of schizophrenia

  • P1-362
  • Da-Zhong Luo:1 Chia-Yuan Chang:1 Tsu-Wei Wang:2 Wen-Sung Lai:1,3,4 
  • 1:Dept Psy, NTU, Taipei, Taiwan (TW) 2:Dept Life Science, NTNU, Taipei, TW 3:Graduate Institute of Brain and Mind Sciences, NTU, Taipei, TW 4:Neurobiology and Cognitive Science Center, NTU, Taipei, TW 

Schizophrenia (SZ) is a severe neuropsychiatric disorder with strong genetic predispositions. Accumulating evidence suggests AKT1 is a susceptibility gene for SZ. Emerging evidence indicates a sex-specific role of Akt1 in modulation of methamphetamine (MA) induced hyperlocomotion, depression-like behavior, sensorimotor gating function, and neuromorphology. Our recent study also revealed Akt1-deficit mice are insensitive to antipsychotic, but GSK3 (key downstream kinase for Akt1) inhibitor had therapeutic potential. Lithium (Li) is a GSK3 inhibitor as a mood-stabilizing drug for bipolar disorder, it is interest to evaluate therapeutic potential of Li on the alleviation of Akt1-related deficits. Taking advantage of P19 embryonal carcinoma cell and Akt1 heterozygous mutant (Akt1+/-) mice as models, a series of experiments was conducted in vitro and in vivo. In study 1, using Ascl1 to differentiate P19 embryonal carcinoma cells into neurons, we examined effect of AKT1/2 inhibitor on neuromarphological alterations in DIV2 and rescue effect of Li. Quantitative analyses of Tuj1-immunostained P19-driven neurons revealed AKT1/2 inhibitor resulted in a 33% reduction of neurite length but no difference in number of differentiated neurons. But reduction of neurite outgrowth was rescued by Li (0.5 & 1 mM). In study 2, based on our previous findings, Akt1+/- female mice and their wild-type littermate controls were used and they received a set of behavioral tasks with chronic treatment of Li (100 mg/kg, ip, twice per day) or saline. Compared to WT controls, Li alleviated behavioral impairments in tail suspension and PPI in Akt1+/- mice. Li also dampened MA-induced stereotypic behaviors in both groups compared to saline controls. Our findings imply therapeutic potential of Li for SZ and GSK3 as a new therapeutic target.

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