Nardostachys jatamansi Targets BDNF-TrkB to Alleviate Ketamine-Induced Schizophrenia-Like Symptoms in Rats

Abstract

Objective: Schizophrenia, a common neurological disorder appearing in the late teens or early adulthood, is characterized by disorganized thinking, behaviour, and perception of emotions. Aberrant N-methyl-<smlcap>D</smlcap>-aspartate (NMDA) receptor-mediated synaptic plasticity is a major pathological event here due to dysfunction of dopamine and glutamate transmission at NMDA receptors. De-regulated brain-derived neurotrophic factor (BDNF), i.e., its signalling through the tropomyosin receptor kinase B (TrkB) receptor, is a major feature of schizophrenia. With recent global awareness of traditional plant medicines in reducing side effects, the aim of our study was to evaluate the efficacy of the ethanolic root extract of a herb belonging to the Valerianacea family, Nardostachys jatamansi, against ketamine-induced schizophrenia-like model in rats. Methods: The effect of the N. jatamansi drug (oral dosage of 500 mg/kg body weight for 14 days) in ketamine-administered male Wistar albino rats (30 mg/kg body weight for 5 days) on modulating behaviour and the level of neurotransmitters like dopamine and glutamate was studied in whole-brain homogenates, and its influence on BDNF and TrkB levels in 2 relevant brain regions, the hippocampus and prefrontal cortex, was assessed. Results: We observed that N. jatamansi treatment exhibited encouraging results in the modulation of ketamine-induced schizophrenia-like behaviours, principally the positive symptoms. Our drug both significantly upregulated the glutamate level and downregulated the dopamine level in whole-brain homogenates and retained the normal levels of BDNF (in the hippocampus but not in the prefrontal cortex) and TrkB (in both hippocampus and prefrontal cortex) induced by ketamine in rats. Conclusion: These findings suggest a neuroprotective effect of the ethanolic root extract of N. jatamansi against ketamine-induced schizophrenia-like symptoms in rats; possibly, regarding its effect on TrkB signalling. Further research is warranted in the treatment of schizophrenic symptoms.

Role of the NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways in the anti-psychotic effects of aripiprazole and sertindole in ketamine-induced schizophrenia-like behaviors in rats

“…The results of our behavioral experiments are consistent with those of previous studies (Boultadakis and Pitsikas 2010;Neill et al 2010;Bolton et al 2012;Chindo et al 2012;Gama et al 2012;Ram et al 2013;Georgiadou et al 2014;Kandratavicius et al 2015;Janardhanan et al 2017;Ibrahim et al 2022), showing that ketamine administration to rats produced schizophrenia-like behavioral changes. Herein, the marked rise in ambulation and rearing frequencies in the open field test revealed ketamineinduced hyperlocomotion.…”