In recent years, piperine has attracted much attention due to its various biological effects as a neuroprotective agent. Therefore, clarification of the possible side effects of piperine is important to identify its potential pharmacological action. The effects of piperine on the long-term plasticity of perforant pathway were studied to dentate gyrus synapses in hippocampus of an animal model of Alzheimer's disease (AD). Adult male rats were injected with intracerebroventricular (ICV) streptozotocin (STZ) bilaterally, on days 1 and 3 (3 mg/kg). The STZ-injected rats were treated with different doses of piperine for 4 weeks before being used in behavioral, electrophysiological and histopathological experiments. The passive-avoidance test was conducted on all animals in order to determine the cognitive performance. Rats were placed in a stereotaxic frame to implant a recording electrode in the hippocampal dentate gyrus and a stimulating electrode in the perforant path. Additionally, we assessed the density of survived neurons stained by cresyl violet. In this study, chronic administration of piperine low dose improved the ICV-STZ induced learning and long-term potentiation (LTP) impairments with no significant effect on baseline synaptic activity. In contrast, remarkable learning and long-term plasticity impairments were observed in rats treated by high dose of piperine in comparison to the other groups. Interestingly, this impaired hippocampal LTP was accompanied by an obvious alteration in baseline activity and significantly decreased neuronal numbers within the hippocampus. Therefore, our data provides a new understanding of the piperine supplementation effects on hippocampal electrophysiological profile although the consequences may be either beneficial or detrimental.

中文翻译：

---

在记忆障碍大鼠模型中，大剂量胡椒碱对海马突触传递和突触可塑性的神经毒性作用。

近年来，胡椒碱作为神经保护剂具有多种生物学作用，因此备受关注。因此，澄清胡椒碱可能的副作用对于确定其潜在的药理作用很重要。研究了胡椒碱对穿孔通路的长期可塑性的影响，以识别阿尔茨海默氏病（AD）动物模型海马中的回突触。成年雄性大鼠在第1天和第3天（3 mg / kg）双侧注射脑室内（ICV）链脲佐菌素（STZ）。在进行行为，电生理和组织病理学实验之前，先将注射了STZ的大鼠用不同剂量的胡椒碱处理4周。为了确定认知能力，对所有动物进行了被动回避测试。将大鼠置于立体定位框架中，以将记录电极植入海马齿状回，并在穿孔路径中植入刺激电极。另外，我们评估了被甲酚紫染色的存活神经元的密度。在这项研究中，长期服用胡椒碱低剂量可改善ICV-STZ诱导的学习和长期增强（LTP）损伤，而对基线突触活性无明显影响。相反，与其他组相比，在用高剂量胡椒碱治疗的大鼠中观察到了显着的学习和长期可塑性损伤。有趣的是，这种受损的海马LTP伴随着基线活动的明显改变和海马内神经元数量的明显减少。因此，