Neurogenesis occurs during the embryological development of the brain. However, it is universally accepted that in all adult mammalian brains, there are two sites of high-density cell division: the subventricular zone of the lateral ventricles (SVZ) and the subgranular zone (SGZ) of the dentate gyrus of the hippocampal formation.

Doxorubicin (DOX) is an anthracycline agent which results in cognitive deterioration and memory impairment, whereas memantine (MEM) is an NMDA receptor antagonist which is approved for the treatment of Alzheimer’s dementia. Many studies have revealed MEM’s positive impact on memory and demonstrated that it stimulates neuronal division in the hippocampus.

This study aimed to assess the effect of MEM on spatial memory and neural proliferation in the hippocampus in adult male rats treated with DOX. For this purpose, forty male Sprague-Dawley rats were divided into four groups of ten rats each according to the agent: control, MEM (2.5 mg/kg), DOX (2 mg/kg), and DOX with MEM. The rats were given seven intraperitoneal injections every other day. We tracked the rat’s weights to assess the weight-reducing effects of the drugs. In order to test spatial memory, the rats were subjected to the novel location recognition (NLR) task 30 minutes after the last injection. Additionally, Ki67 immunohistochemistry was performed to examine hippocampal proliferation.

The results showed a significant reduction in discrimination index (DI) in the DOX-treated group compared to MEM- (p < 0.001) and MEM with DOX-treated groups (p < 0.001). There was a significant increase in Ki67-positive cells in the MEM-treated group compared to the saline-treated group. Treatment with DOX impaired hippocampal proliferation compared to treatment with MEM or saline. The co-administration of MEM with DOX ameliorated the decline in hippocampal proliferation compared to treatment with DOX alone. There was a significant weight reduction in the DOX group in comparison to the control group, but MEM attenuated DOX-induced weight loss.

Rats treated with DOX displayed a drop in memory, hippocampal proliferation, and weight compared to the MEM-treated group, whereas the co-administration of MEM with DOX protected memory, hippocampal proliferation, and doxorubicin-induced weight loss.

中文翻译：

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美金刚改善成年雄性大鼠的记忆力和海马增殖

神经发生发生在大脑的胚胎发育过程中。然而，普遍认为，在所有成年哺乳动物的大脑中，都有两个高密度细胞分裂部位：侧脑室的脑室下区（SVZ）和海马结构齿状回的颗粒下区（SGZ）。

多柔比星 (DOX) 是一种蒽环类药物，可导致认知退化和记忆障碍，而美金刚 (MEM) 是一种 NMDA 受体拮抗剂，被批准用于治疗阿尔茨海默氏症。许多研究揭示了 MEM 对记忆的积极影响，并证明它可以刺激海马中的神经元分裂。

本研究旨在评估 MEM 对接受 DOX 治疗的成年雄性大鼠海马空间记忆和神经增殖的影响。为此，将 40 只雄性 Sprague-Dawley 大鼠根据药剂分为四组，每组 10 只大鼠：对照、MEM (2.5 mg/kg)、DOX (2 mg/kg) 和 DOX 与 MEM。每隔一天对大鼠进行七次腹腔注射。我们跟踪大鼠的体重以评估药物的减肥效果。为了测试空间记忆，大鼠在最后一次注射后 30 分钟接受了新的位置识别 (NLR) 任务。此外，还进行了 Ki67 免疫组织化学检查以检查海马增殖。

结果显示，与 MEM- (p < 0.001) 和 MEM 与 DOX 治疗组 (p < 0.001) 相比，DOX 治疗组的辨别指数 (DI) 显着降低。与盐水处理组相比，MEM处理组中Ki67阳性细胞显着增加。与用 MEM 或盐水治疗相比，用 DOX 治疗会损害海马增殖。与单独使用 DOX 治疗相比，MEM 与 DOX 的共同给药改善了海马增殖的下降。与对照组相比，DOX 组的体重显着减轻，但 MEM 减弱了 DOX 引起的体重减轻。

与 MEM 治疗组相比，用 DOX 治疗的大鼠表现出记忆力、海马增殖和体重下降，而 MEM 与 DOX 的共同给药保护了记忆、海马增殖和阿霉素诱导的体重减轻。