小檗碱改善氯胺酮诱导精神分裂症弓形虫感染大鼠模型的抑制性回避记忆障碍。

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

机构信息

Students Research Committee, Public Health School, Ardabil University of Medical Sciences, Ardabil, Iran.

Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

BMC Complement Med Ther. 2023 Aug 30;23(1):303. doi: 10.1186/s12906-023-04107-4.

DOI:10.1186/s12906-023-04107-4

PMID:37649038

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10469906/

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.

摘要

背景

弓形虫感染引起的记忆障碍已有文献记载。小檗碱（BRB）以其增强记忆的作用而闻名，并且已显示出有前景的结果。然而，BRB 对弓形虫感染和精神分裂症引起的巩固和再巩固记忆障碍的影响尚不清楚。在这里；我们研究了 BRB 对弓形虫感染引起的抑制性回避（IA）记忆巩固和再巩固障碍的影响，以及作为精神分裂症药理学模型的氯胺酮（Ket）。还；分析了内侧前额叶皮质（mPFC）和海马中的脑源性神经营养因子（BDNF）水平。

方法

用 RH 株弓形虫感染大鼠或连续 5 天腹腔内（i.p）给予 Ket（30 mg/kg/天）（作为精神分裂症模型）。然后口服 BRB（25 mg/kg/天）连续 5 天。最后，在 48 个条件后进行 IA 记忆保留测试，并测量 BDNF。

结果

结果表明，弓形虫感染动物的 IA 记忆受损，因为与对照组动物相比，观察到较低的步穿潜伏期（STL）。我们发现，在感染和 Ket 处理的大鼠中，BRB 给药后 STL 显著升高（P=0.01，P=0.001），在暗区的总时间显著减少（P=0.001），表明巩固和再巩固记忆得到改善（STL 增加）。此外，BDNF 水平在弓形虫感染和 Ket 诱导组的海马和 mPFC 区域均降低（P=0.01），BRB 治疗后显著升高。此外；我们发现，BRB 给药显著增加了 mPFC 中 mPFC（P<0.01）和海马（P=0.001）的 BDNF 水平，在 Ket 处理和感染弓形虫的大鼠中。