Gáspárová Zdenka, Snirc Vladimír, Stolc Svorad
Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, SK-84104 Bratislava, Slovak Republic.
Interdiscip Toxicol. 2011 Mar;4(1):56-61. doi: 10.2478/v10102-011-0011-0.
Previously, the pyridoindole SMe1EC2 was proved to inhibit lipoperoxidation and carbonylation of proteins in rat brain cortex in the system Fe(2+)/ascorbate and improvement of resistance of the rat hippocampus was reported against ischemic conditions in vitro (hypoxia/hypoglycemia) expressed by the enhanced neuronal response recovery in reoxygenation. The hippocampus fulfils many of the criteria for a neuronal correlate of learning and memory. Recently, an impairment of hippocampal long-term potentiation (LTP) was reported under oxidative stress. Different therapies, including antioxidants, have been studied intensively concerning the impairment of neuronal plasticity. In this study marked reduction of LTP, elicited by a single burst (100 Hz, 1s) in the CA3-CA1 area of rat hippocampal slices, was shown due to transient hypoxia/hypoglycemia compared to control slices. On the basis of previously reported antioxidant and neuroprotective effects of SMe1EC2, its effect on loss of LTP in the hippocampus due to ischemic conditions was studied in vitro. The pyridoindole tested improved hypoxia/hypoglycemia-induced reduction of LTP compared to untreated hypoxic slices. An opposite effect of SMe1EC2 on LTP induction was found in control slices. The mechanism of SMe1EC2 action on LTP in ischemic conditions has been suggested to differ from the mechanism of its effect in "normoxia" and may be due to different redox status in control and ischemic brain tissue. The manifested LTP-protective effect of SMe1EC2 observed in the rat hippocampus exposed to ischemia in vitro may find exploitation in therapy associated with injured neuronal plasticity in some conditions, including ischemia, trauma and aging in man.
此前，已证明吡啶并吲哚SMe1EC2在Fe(2+)/抗坏血酸体系中可抑制大鼠脑皮质中蛋白质的脂质过氧化和羰基化，并且有报道称其可提高大鼠海马体对体外缺血条件（缺氧/低血糖）的抗性，表现为复氧时神经元反应恢复增强。海马体满足学习和记忆的神经元关联的许多标准。最近，有报道称在氧化应激下海马体长时程增强（LTP）受损。针对神经元可塑性受损的情况，人们对包括抗氧化剂在内的不同疗法进行了深入研究。在本研究中，与对照切片相比，由于短暂的缺氧/低血糖，大鼠海马体切片CA3-CA1区域单次爆发（100Hz，1s）引发的LTP显著降低。基于先前报道的SMe1EC2的抗氧化和神经保护作用，研究了其对缺血条件下海马体LTP丧失的影响。与未处理的缺氧切片相比，所测试的吡啶并吲哚改善了缺氧/低血糖诱导的LTP降低。在对照切片中发现SMe1EC2对LTP诱导有相反的作用。有人认为SMe1EC2在缺血条件下对LTP的作用机制与其在“常氧”条件下的作用机制不同，可能是由于对照脑组织和缺血脑组织的氧化还原状态不同。在体外暴露于缺血的大鼠海马体中观察到的SMe1EC2明显的LTP保护作用，可能在与某些情况下受损的神经元可塑性相关的治疗中得到应用，这些情况包括人类的缺血、创伤和衰老。
