Kotti T, Halonen T, Sirviö J, Riekkinen P, Miettinen R
Department of Neuroscience and Neurology and A.I. Virtanen Institute, University of Kuopio, Finland.
Neuroscience. 1997 Sep;80(1):105-17. doi: 10.1016/s0306-4522(97)00128-0.
Nitric oxide has been postulated as a retrograde intercellular messenger for long-term potentiation, a form of synaptic plasticity that is associated with learning and memory processes. In the present study we investigated whether the loss or survival of nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-containing neurons, which are known to synthesize nitric oxide, would be an useful indicator for evaluating the structural and functional state of the rat hippocampus after status epilepticus that is induced by intraperitoneal injection of kainic acid. Besides NADPH diaphorase histochemistry, two other histological parameters were studied: the grade of cell damage evaluated from silver-impregnated sections, and the number of somatostatin-containing neurons in different hippocampal subfields. We found that the number of NADPH diaphorase-containing neurons in the hilus and granule cell layer correlated well with spatial learning and memory performance as assessed by the Morris water-maze test. The extent of cell damage in the CA1 subfield analysed in silver-impregnated sections and the number of hilar somatostatin-containing neurons also significantly correlated with latencies in the water-maze test. Furthermore, linear regression analysis revealed that the number of somatostatin-containing neurons in the hilus explains about 50% of the variation in water-maze learning. These findings emphasize that although general structural preservation is of crucial importance for the function of the hippocampus also interneurons, such as somatostatin- and NADPH diaphorase-containing neurons, may play an important role during the acquisition phase and processing of information in hippocampal circuitry. Therefore, in addition to evaluating general cell damage, analysis of the cell loss that occurs in the interneuron subpopulations will be beneficial in verifying structural and functional deficits of the hippocampus after status epilepticus.
一氧化氮被认为是一种用于长时程增强的逆行性细胞间信使,长时程增强是一种与学习和记忆过程相关的突触可塑性形式。在本研究中,我们调查了已知可合成一氧化氮的含烟酰胺腺嘌呤二核苷酸磷酸(NADPH)黄递酶的神经元的丢失或存活情况,是否会成为评估腹腔注射红藻氨酸诱导癫痫持续状态后大鼠海马结构和功能状态的有用指标。除了NADPH黄递酶组织化学,还研究了另外两个组织学参数:从银染切片评估的细胞损伤程度,以及不同海马亚区中含生长抑素的神经元数量。我们发现,通过莫里斯水迷宫试验评估,海马门区和颗粒细胞层中含NADPH黄递酶的神经元数量与空间学习和记忆表现密切相关。在银染切片中分析的CA1亚区的细胞损伤程度以及海马门区含生长抑素的神经元数量也与水迷宫试验中的潜伏期显著相关。此外,线性回归分析显示,海马门区含生长抑素的神经元数量可解释水迷宫学习中约50%的变异性。这些发现强调,虽然一般结构的保存对海马功能至关重要,但中间神经元,如含生长抑素和NADPH黄递酶的神经元,在海马回路信息获取阶段和处理过程中可能也发挥重要作用。因此,除了评估一般细胞损伤外,分析中间神经元亚群中发生的细胞丢失将有助于验证癫痫持续状态后海马的结构和功能缺陷。