Cognitive impairment in spontaneously hypertensive rats: role of central nicotinic receptors .1.
Cognitive impairment in spontaneously hypertensive rats: role of central nicotinic receptors .1.
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DOI：
10.1016/s0006-8993(97)00793-2
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发表时间：
1997-10-10
期刊：
影响因子：
2.9
通讯作者：
Buccafusco, JJ
中科院分区：
文献类型：
--
作者：
Gattu, M;Pauly, JR;Buccafusco, JJ
人类原发性高血压和遗传诱导的大鼠高血压都与一系列认知能力障碍有关。自发性高血压大鼠（SHR）的脑烟碱乙酰胆碱受体表达减少，这一因素可能在该品系在学习和记忆相关任务中的表现受损中发挥作用。为了确定SHR的任务损害是否与中央烟碱乙酰胆碱受体的表达减少有关，本研究采用水迷宫（空间记忆）任务两阶段测试了12周龄SHR的表现，并与Wistar Kyoto （WKY）和Wistar两种年龄匹配的正常血压品系大鼠进行了比较。在第一阶段，与WKY或Wistar大鼠相比，SHR表现出明显增加的定位隐藏平台的潜伏期。在第2阶段（4天间隔期后的后续一系列试验）中，大鼠被要求找到一个新的平台位置，与正常血压的菌株相比，SHR再次表现出明显的性能受损。在单次被动回避范式中，与WKY和Wistar大鼠相比，SHR再次表现出显著减少的回避行为。在连续的冠状面切片中，SHR中[H-3]胞氨酸结合位点的密度在大约一半的被检查的大脑区域中下降了高达25%，在头侧区域的缺陷尤其明显。[I-125] α -班加罗毒素与SHR脑组织的结合也减少；然而，只有某些脑区表现出显著的种间差异。SHR中烟碱受体亚型表达的这些变化不是由于胆碱能神经元密度的变化，因为标记泡状乙酰胆碱转运体的[H-3]维酰胺的结合密度在品系间没有差异。此外，与血压正常的大鼠相比，尼古丁刺激的皮质和纹状体突触体的铷外排量在体外明显减少。这些结果与SHR皮层尼古丁受体表达减少在该品系的空间和非空间学习和记忆相关任务的表现受损中起作用的可能性是一致的。(C) 1997爱思唯尔科学有限公司
Both human essential hypertension and genetically induced hypertension in rats have been associated with a range of impairments of cognitive ability. The spontaneous hypertensive rat (SHR) previously has been shown to exhibit a decrease in the expression of brain nicotinic acetylcholine receptors, a factor that could play a role in the impaired ability of this strain in the performance of learning and memory-related tasks. The purpose of this study was to help determine whether task impairment by SHR was related to the reduced expression of central nicotinic acetylcholine receptors, Twelve-week-old SHR were tested in two phases of a water maze (spatial memory) task, and their performance was compared with that of two age-matched normotensive strains, Wistar Kyoto (WKY) and Wistar rats. During Phase 1, SHR exhibited significantly increased latencies to locate a hidden platform as compared with either WKY or Wistar rats. During Phase 2 (subsequent series of trials after a 4-day inter-phase period), where rats were required to find a new platform location, SHR again exhibited significantly impaired performance compared to the normotensive strains. In a single trial passive avoidance paradigm, SHR again displayed significantly reduced avoidance behavior as compared with both WKY and Wistar rats. In consecutive coronal sections, the density of [H-3]cytisine binding sites was decreased in SHR by up to 25% in about half of the brain regions examined, with the deficits particularly apparent in cephalic regions. The binding of [I-125]alpha-bungarotoxin to brain sections also was decreased in SHR; however, only certain brain areas exhibited significant interstrain differences. These alterations in the expression of putative nicotinic receptor subtypes in SHR were not due to changes in the density of cholinergic neurons since there were no interstrain differences in the binding densities for [H-3]vesamicol, which labels the vesicular acetylcholine transporter. Moreover, the magnitude of nicotine-stimulated rubidium efflux from cortical and striatal synaptosomes in vitro was significantly reduced in samples derived from SHR as compared with those from normotensive rats. These results are consistent with the possibility that a reduction in the expression of cortical nicotinic receptors in SHR plays a role in this strain's impaired performance of both spatial and non-spatial learning and memory-related tasks. (C) 1997 Elsevier Science B.V.