Maćkowiak Marzena, Chocyk Agnieszka, Markowicz-Kula Katarzyna, Wedzony Krzysztof
Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, 12 Smetna Street, Poland.
Brain Res. 2007 May 7;1148:43-52. doi: 10.1016/j.brainres.2007.02.014. Epub 2007 Feb 17.
Recent evidence indicates that the polysialylated neural cell adhesion molecule (PSA-NCAM) is involved in hippocampal plasticity. On the other hand, CB1 receptor activation is known to disturb some hippocampal processes involving plastic changes, such as learning and memory. Therefore, the present study investigated the effect of HU-210, a CB1 receptor agonist, on the expression of PSA-NCAM protein in the dentate gyrus (DG) and CA3 region of the rat hippocampus. It was found that at a dose of 0.1 mg/kg i.p. of HU-210, the number of PSA-NCAM immunoreactive (IR) cells in the DG declined in a time-dependent manner. The decrease in PSA-NCAM expression was observed at 1 and 2 days (ca. 21% and 30%, respectively), but not after 4 h and 4 days following HU-210 administration. However, HU-210 treatment did not change the length density of PSA-NCAM immunopositive processes in CA3 mossy fibers at all the time points measured. The effect observed in the DG on day 2 was blocked by AM-251 (1 mg/kg, i.p.), a CB1 receptor antagonist, given 30 min before HU-210. Neither the number of Ki-67 (IR) cells (a marker of proliferation) nor the number of doublecortin-IR cells (a marker of immature neurons) was affected by HU-210 (0.1 mg/kg, i.p.) treatment at any of the time points. An analysis of co-localization of CB1 receptor protein with PSA-NCAM protein revealed that both proteins were not present in the same population of neurons in the subgranular layer of the DG. The observed changes in PSA-NCAM expression were not related to the reduction of proliferation or differentiation of newly born cells, but were possible due to alternations in the synaptic activity in the DG. However, such alteration in the PSA-NCAM expression may change the timing of the functional maturation of newly born neurons. Moreover, the above finding suggests that acute activation of CB1 receptors may result in the stiffening of the hippocampal structure and susceptibility to plastic changes and may lead to functional impairment governed by alterations in the hippocampal structure.
近期证据表明，多唾液酸神经细胞黏附分子（PSA-NCAM）参与海马可塑性。另一方面，已知CB1受体激活会干扰一些涉及可塑性变化的海马过程，如学习和记忆。因此，本研究调查了CB1受体激动剂HU-210对大鼠海马齿状回（DG）和CA3区PSA-NCAM蛋白表达的影响。研究发现，腹腔注射0.1 mg/kg剂量的HU-210后，DG中PSA-NCAM免疫反应性（IR）细胞数量呈时间依赖性下降。在给药后1天和2天观察到PSA-NCAM表达下降（分别约为21%和30%），但在4小时和4天后未观察到下降。然而，在所有测量时间点，HU-210处理均未改变CA3苔藓纤维中PSA-NCAM免疫阳性突起的长度密度。在HU-210给药前30分钟腹腔注射CB1受体拮抗剂AM-251（1 mg/kg）可阻断在第2天DG中观察到的效应。在任何时间点，HU-210（0.1 mg/kg，腹腔注射）处理均未影响Ki-67（IR）细胞数量（增殖标志物）和双皮质素-IR细胞数量（未成熟神经元标志物）。CB1受体蛋白与PSA-NCAM蛋白的共定位分析显示，这两种蛋白不存在于DG颗粒下层同一群神经元中。观察到的PSA-NCAM表达变化与新生细胞增殖或分化的减少无关，而可能是由于DG中突触活动的改变。然而，PSA-NCAM表达的这种改变可能会改变新生神经元功能成熟的时间。此外，上述发现表明，CB1受体的急性激活可能导致海马结构僵化以及对可塑性变化的易感性，并可能导致由海马结构改变所支配的功能损害。
