Resveratrol Reverses Social Deficits and Metabolic Dysfunction of Mice Model for Negative Symptoms of Schizophrenia

Abstract

The negative symptoms of schizophrenia without effective therapeutic agents seriously affect the quality of life. Studies investigating the neurobiological mechanisms of the negative symptoms of schizophrenia failed to provide a unanimous conclusion, but generally accepted to be related to the prefrontal cortex (PFC). Resveratrol is a kind of natural plant polyphenol and has a potential role in negative symptoms treatment for its neuroprotective effects. To investigate the metabolic mechanism of the negative symptoms and the therapeutic effect of resveratrol on it, we analyzed the metabolic changes in the PFC of MK-801-induced schizophrenia model using ex vivo ¹H nuclear magnetic resonance spectroscopy. And then, after chromic administration of resveratrol, we tested the social interaction behaviors of the schizophrenia model and analyzed the metabolic changes in the PFC. Our results showed that the levels of alanine (Ala), glutamate (Glu), tautine (Tau), glynine (Gly), choline (Cho), and valine (Val) are significantly decreased compared to control animals. The social deficits of MK-801-treated mice are improved after resveratrol administration. And the levels of Glu, Gly, and Cho were reversed after the treatment of resveratrol. In conclusion, our results suggest that the negative symptoms are associated with decreased concentration of Ala, Glu, Tau, Gly, Cho, Val in PFC and the social deficits could be recovered by resveratrol treatment, as well as the levels of Glu, Gly, and Cho in PFC.

Keywords:

• Schizophrenia
• negative symptoms
• social deficits
• ex vivo ¹H nuclear magnetic resonance spectroscopy
• resveratrol

Additional information

Funding

This work is financially supported by the National Natural Science Foundation of China (21874078, 22074072), the Taishan Young Scholar Program of Shandong Province (tsqn20161027), the Major Science and Technology Innovation Project of Shandong Province (2018CXGC1407), the Key Research and Development Project of Shandong Province (2016GGX102028, 2016GGX102039, 2017GGX20111), and the First Class Discipline Project of Shandong Province.