Evaluation of the Effect of Peripheral Injection of Leptin on Spatial Memory

S. Rasi; G. Mohaddes; N. Naghdi; M. Ilkhani Pour; V. Hajali

摘要

Introduction: Leptin is a peptide hormone secreted by adipose tissue. Some studies have also suggested that leptin affect learning and memory. The hippocampus has been implicated in many learning and memory functions including spatial memory. The present study is scheduled to investigate the effect of intraperitoneal (IP) injection of different doses of leptin on spatial memory formation. Material and methods: 60 male rats were divided into 6 groups in our experiments: (1) control, (2) sham, and (3), (4), (5), (6) intraperitoneal injection of 0.05, 0.1, 0.25 and 0.5 mg/kg doses of leptin respectively. All groups were trained in Morris water maze for two days. Learning parameters were compared among groups. Results: Our results showed, there were significant differences of learning parameters between sham group and test groups in spatial learning. Conclusion: In conclusion, our findings suggest that intraperitoneally injection of leptin improved spatial memory in rat. Leptin shows its highest effect with medium doses. Introduction Leptin is a hormone that regulates body weight and energy homeostasis via its actions on specific hypothalamic nuclei (1). Leptin is the product of the obese (ob) gene that is synthesized predominantly, although not exclusively, by white adipose tissue (2). Adipocytes secrete leptin into the blood. As it circulates through the cerebrovasculature, transporters for leptin carry it across the BBB to enter the interstitial fluid of the brain (3, 4). Leptin functions are thought to occur through the leptin receptors mainly in the hypothalamic nuclei. However, leptin receptors exist throughout the brain including the hippocampus (5). Immunoreactivity for leptin receptors has been found in the hippocampus especially in the dentate gyrus and CA1 (6). Moreover, it has been demonstrated that leptin receptor-deficient animals show impaired LTP in CA1 and poor spatial memory. In the Morris water-maze test, their poor performances in the invisible-platform situation may suggest a spatial memory deficit in both Zucker fatty rats and db/db mice (7).The hippocampus has a well-documented role in spatial memory acquisition (8). It has been also determined that hippocampus has an essential role in rodent spatial memory and navigation (9). Hippocampal lesions produce memory deficits, but since hippocampal lesions do not eradicate previously established memory traces, the hippocampus could be a temporary store for information, particularly spatial information that is subsequently encoded in other cortical regions (10). Some studies have been conducted on leptin effect on different type of learning and memory.Farr and colleagues reported the role of leptin in learning and memory using an animal model. They found that mice navigated a maze better after they received leptin. Their research indicated that administration of leptin to mice improved retention of T-maze footshock avoidance and step down inhibitory avoidance (5). In addition, Oomura et al. showed a facilitation effect on learning and memory performance in passive avoidance and Morris water maze task after daily intravenous injection of leptin (50 ηg/kg) in rats (11). The other study suggested that leptin applied directly into the dentate gyrus; enhanced normal LTP at 1.0 ηM but inhibited LTP at lower and higher doses in the Morris water maze in urethane anesthetized rats (6). Just one experiment reported that leptin exhibit no effect on memory processes (11). Since only a few studies investigated the involvement of systemic leptin in spatial memory formation and the subject is somehow controversial, we decided to assess the effect of different doses of intraperitoneal leptin on spatial memory in a Morris water maze task. Material and Method Animals and substances. Adult male Wistar rats (220–250 g, aged 12 week) were obtained from colony of Tabriz university of Medical Sciences. They were housed in a temperature (22 ± 2° C) and humidity-controlled room. The animal

机译：简介：瘦素是脂肪组织分泌的一种肽激素。一些研究还表明，瘦素会影响学习和记忆。海马已经牵涉到许多学习和记忆功能，包括空间记忆。本研究计划调查腹膜内（IP）注射不同剂量的瘦素对空间记忆形成的影响。材料和方法：在我们的实验中将60只雄性大鼠分为6组：（1）对照，（2）假手术和（3），（4），（5），（6）腹腔注射0.05、0.1、0.25和分别为0.5 mg / kg的瘦素剂量。所有组在莫里斯水迷宫中接受了为期两天的培训。在各组之间比较学习参数。结果：我们的结果显示，在空间学习中，假组和测试组之间的学习参数存在显着差异。结论：总之，我们的发现表明腹膜内注射瘦素可改善大鼠的空间记忆。瘦素在中等剂量下显示出最高的作用。简介瘦素是一种激素，通过作用于特定的下丘脑核来调节体重和能量稳态（1）。瘦素是肥胖（ob）基因的产物，主要但非排他性地由白色脂肪组织合成（2）。脂肪细胞将瘦蛋白分泌到血液中。当它在脑血管系统中循环时，瘦素的转运蛋白会使其穿过BBB进入大脑的间质液（3、4）。瘦素功能被认为主要通过下丘脑核中的瘦素受体发生。然而，瘦素受体存在于包括海马在内的整个大脑中（5）。瘦素受体的免疫反应性已在海马中发现，尤其是在齿状回和CA1中（6）。而且，已经证明瘦蛋白受体缺陷的动物在CA1中显示出LTP受损和差的空间记忆。在莫里斯水迷宫测试中，它们在隐形平台情况下的不良表现可能表明扎克脂肪大鼠和db / db小鼠均存在空间记忆缺陷（7）。 8）。还已经确定海马在啮齿动物的空间记忆和导航中起着至关重要的作用（9）。海马损伤会产生记忆缺陷，但是由于海马损伤不会根除先前建立的记忆痕迹，因此海马可能是信息的临时存储，尤其是随后在其他皮质区域编码的空间信息（10）。瘦素对不同类型的学习和记忆的影响已经进行了一些研究。Farr和同事使用动物模型报道了瘦素在学习和记忆中的作用。他们发现，接受瘦素的小鼠在迷宫中的导航更好。他们的研究表明，向小鼠施用瘦素可改善避免T型迷宫踩踏和避免抑制性退缩的保持力（5）。此外，Oomura等。在每天静脉注射瘦素（50ηg/ kg）后，在被动回避和莫里斯水迷宫任务中显示出对学习和记忆表现的促进作用（11）。另一项研究表明，瘦素可直接应用于齿状回。在经尿烷麻醉的大鼠中，Morris水迷宫中的LTP在1.0ηM时可增强正常LTP，但在低剂量和高剂量下均可抑制LTP（6）。仅有一项实验报道瘦素对记忆过程没有影响（11）。由于只有少数研究调查了系统性瘦素在空间记忆形成中的参与，并且该受试者存在某种争议，因此我们决定在莫里斯水迷宫任务中评估不同剂量的腹膜内瘦素对空间记忆的影响。材料和方法动物和物质。成年雄性Wistar大鼠（220–250 g，年龄12周）从Tabriz医科大学的殖民地获得。他们被安置在一个温度（22±2℃）和湿度控制的房间。这个动物

Evaluation of the Effect of Peripheral Injection of Leptin on Spatial Memory

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