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. 2023 Dec;37(12):5904-5915.
doi: 10.1002/ptr.8002. Epub 2023 Aug 31.

Effect of D-pinitol on MK-801-induced schizophrenia-like behaviors in mice

Jae Youn Kim  1 , Chang Hyeon Kong  2 , Do Yeon Kim  2 , Ji Won Min  2 , Keontae Park  2 , Mijin Jeon  2 , Woo Chang Kang  2 , Seo Yun Jung  2 , Jong Hoon Ryu  1   2   3
Affiliations

Effect of D-pinitol on MK-801-induced schizophrenia-like behaviors in mice

Jae Youn Kim et al. Phytother Res. 2023 Dec.

Abstract

Schizophrenia is a chronic brain disorder characterized by positive symptoms (delusions or hallucinations), negative symptoms (impaired motivation or social withdrawal), and cognitive impairment. In the present study, we explored whether D-pinitol could ameliorate schizophrenia-like behaviors induced by MK-801, an N-methyl-D-aspartate receptor antagonist. Acoustic startle response test was conducted to evaluate the effects of D-pinitol on sensorimotor gating function. Social interaction and novel object recognition tests were employed to measure the impact of D-pinitol on social behavior and cognitive function, respectively. Additionally, we examined whether D-pinitol affects motor coordination. Western blotting was conducted to investigate the mechanism of action of D-pinitol. Single administration of D-pinitol at 30, 100, or 300 mg/kg improved the sensorimotor gating deficit induced by MK801 in the acoustic startle response test. D-Pinitol also reversed social behavior deficits and cognitive impairments induced by MK-801 without causing any motor coordination deficits. Furthermore, D-pinitol reversed increased expression levels of pNF-kB induced by MK-801 treatment and consequently increased expression levels of TNF-α and IL-6 in the prefrontal cortex. These results suggest that D-pinitol could be a potential candidate for treating sensorimotor gating deficits and cognitive impairment observed in schizophrenia by down-regulating transcription factor NF-κB and pro-inflammatory cytokines in the prefrontal cortex.

Keywords: D-Pinitol; MK-801; novel object recognition test; prepulse inhibition; schizophrenia; social interaction.

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References

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