孕酮在海人酸给药前给药可防止在 Morris 水迷宫中认知表现的下降。
Progesterone, administered before kainic acid, prevents decrements in cognitive performance in the Morris Water Maze.
机构信息
Department of Psychology, The University at Albany-SUNY, 1400 Washington Avenue, Albany, New York 12222, USA.
出版信息
Dev Neurobiol. 2011 Feb;71(2):142-52. doi: 10.1002/dneu.20832.
The nature of progesterone (P₄)'s neuroprotective effects is of interest. We investigated effects of P₄ when administered before, or after, kainic acid, which produces ictal activity and damage to the hippocampus, to mediate effects on spatial performance. The hypothesis was that P₄, compared with vehicle, would reduce decrements in Morris Water Maze performance induced by kainic acid. Experiment 1: We examined the effects of kainic acid on plasma stress hormone, corticosterone, and progestogen (P₄ and its metabolites) levels in plasma and the hippocampus after subcutaneous (s.c.) P₄ administration to ovariectomized rats. Rats administered kainic acid had the highest corticosterone levels immediately following injection. P₄ is 5α-reduced to dihydroprogesterone (DHP) and subsequently metabolized to 5α-pregnan-3α-ol-20-one (3α,5α-THP) by 3α-hydroxysteroid dehydrogenase. The regimen of P₄ used produced circulating and hippocampal levels of P₄, DHP, and 3α,5α-THP within a physiological range, which declined at 14 hours postinjection and were not altered by kainic acid. Experiment 2: The physiological P₄ regimen was administered to rats before, or after, kainic acid-induced seizures, and later effects on water maze performance were compared with that of rats administered vehicle. Rats administered kainic acid had significantly poorer performance in the water maze (i.e., increased latencies and distances to the hidden platform) than did rats administered vehicle. Administration of P₄ before, but not after, kainic acid prevented these performance deficits. Thus, these data suggest that a physiological regimen of P₄ can prevent some of the deficits in water maze performance produced by kainic acid.
孕激素（P₄）的神经保护作用性质是研究的热点。我们研究了 P₄ 在给予前或给予后对海人酸（导致癫痫发作和海马损伤）的影响，以调节对空间性能的影响。假设是 P₄与载体相比，会减少海人酸引起的水迷宫表现的下降。实验 1：我们研究了海人酸对去卵巢大鼠皮下（s.c.）给予 P₄ 后血浆应激激素皮质酮和孕激素（P₄及其代谢物）水平以及海马的影响。给予海人酸的大鼠在注射后立即具有最高的皮质酮水平。P₄ 被 5α-还原为二氢孕酮（DHP），然后被 3α-羟甾族脱氢酶代谢为 5α-孕烷-3α-醇-20-酮（3α,5α-THP）。使用的 P₄方案产生了循环和海马中的 P₄、DHP 和 3α,5α-THP 水平，在注射后 14 小时下降，并且不受海人酸的影响。实验 2：生理 P₄ 方案在海人酸诱导的癫痫发作前或发作后给予大鼠，然后比较对水迷宫表现的影响与给予载体的大鼠。给予海人酸的大鼠在水迷宫中的表现明显较差（即潜伏期和到达隐藏平台的距离增加），而给予载体的大鼠则不然。给予 P₄ 前，而不是给予海人酸后，可预防这些表现缺陷。因此，这些数据表明，生理 P₄ 方案可以预防海人酸引起的水迷宫表现缺陷的一些。
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