Berberine improves inhibitory avoidance memory impairment of Toxoplasma gondii-infected rat model of ketamine-induced schizophrenia

Abstract

Background Memory impairment caused by Toxoplasma gondii infection has been documented. Berberine (BRB) is well known for its enhancing effects on memory and has shown promising results. However, the impact of BRB on T. gondii infection and schizophrenia-induced consolidation and reconsolidation memory impairment is still unclear. Here; we examined the effect of BRB on the inhibitory avoidance (IA) memory consolidation and reconsolidation impairment induced by T. gondii infection, and ketamine (Ket) as a pharmacological model of schizophrenia. Also; the brain-derived neurotrophic factor (BDNF) levels in the medial prefrontal cortex (mPFC) and hippocampus were analyzed. Methods Rats were infected with T. gondii RH strain or received Ket (30 mg/kg/day) intraperitoneally (i.p) for at least five consecutive days (as the model of schizophrenia). Then followed by oral administration with BRB (25 mg/kg/day) for five days. Finally, the IA memory retention test was examined 48 post-conditioning, and BDNF was measured. Results Results indicated IA memory impairment in T. gondii-infected animals since lower step-through latency (STL) was observed than in control animals. We found significant (P = 0.01, P = 0.001) elevations in STL and a significant decrease (P = 0.001) in total time spent in the dark area following BRB administration in infected and Ket-treated rats, indicating improvement (increased STL) in consolidation and reconsolidation memory. Moreover, BDNF levels were reduced (P = 0.01) in the hippocampus and mPFC regions of both T. gondii- infected and Ket-induced groups, which remarkably enhanced after BRB treatment. Furthermore; we found that BRB administration notably increased the mPFC BDNF levels in mPFC (P < 0.01) and hippocampus (P = 0.001) in the Ket-treated and rats infected with T. gondii. Conclusion Taken together; BRB may be a valuable preclinical treatment for improving memory impairment through BDNF expression in PFC and hippocampus, therefore; BRB is suggested for memory disturbances induced by T. gondii infection.

Research progress on antidepressant effects and mechanisms of berberine

“…However, after acute dosing, psychiatric, psychotomimetic, cardiovascular, neurological, and other side-effects were more commonly observed after ketamine treatment than after placebo in patients with depression ( Short et al, 2018 ). Interestingly, one study showed Ber can inhibit avoidance memory impairment of Toxoplasma gondii-infected rat model of ketamine-induced schizophrenia ( Gholizadeh et al, 2023 ). Meanwhile, levo -tetrahydropalmatine, one of tetrahydroprotoberberines, could increase the bioavailability of ketamine and promote the metabolism of ketamine ( Du et al, 2020 ), so the combination of ketamine and Ber might be a valuable new idea.…”

Revolutionizing Ischemic Stroke Diagnosis and Treatment: The Promising Role of Neurovascular Unit-Derived Extracellular Vesicles

“…Additionally, astrocyte-derived EVs could promote recovery after IS by reducing the infarct volume, protecting the function of neuronal tracts, promoting axonal regeneration, and enhancing compound action potential recovery [123]. Recently, a large number of studies proved that berberine had neuroprotective effects on central nervous system diseases, including IS, AD, PD, and schizophrenia [124][125][126][127]. There are even two clinical studies on the efficacy of berberine in the treatment of schizophrenia (NCT02983188, NCT03548155: https://clinicaltrials.gov, accessed on 7 March 2024).…”

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