Benedict Christian, Hallschmid Manfred, Hatke Astrid, Schultes Bernd, Fehm Horst L, Born Jan, Kern Werner
Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, Haus 23a, 23538 Lübeck, Germany.
Psychoneuroendocrinology. 2004 Nov;29(10):1326-34. doi: 10.1016/j.psyneuen.2004.04.003.
Previous studies have suggested an acutely improving effect of insulin on memory function. To study changes in memory associated with a prolonged increase in brain insulin activity in humans, here we used the intranasal route of insulin administration known to provide direct access of the substance to the cerebrospinal fluid compartment. Based on previous results indicating a prevalence of insulin receptors in limbic and hippocampal regions as well as improvements in memory with systemic insulin administration, we expected that intranasal administration of insulin improves primarily hippocampus dependent declaration memory function. Also, improvements in mood were expected. We investigated the effects of 8 weeks of intranasal administration of insulin (human regular insulin 4 x 40 IU/d) on declarative memory (immediate and delayed recall of word lists), attention (Stroop test), and mood in 38 healthy subjects (24 males) in a double blind, between-subject comparison. Blood glucose and plasma insulin levels did not differ between the placebo and insulin conditions. Delayed recall of words significantly improved after 8 weeks of intranasal insulin administration (words recalled, Placebo 2.92 +/- 1.00, Insulin 6.20 +/- 1.03, p < 0.05). Moreover, subjects after insulin reported signs of enhanced mood, such as reduced anger (p < 0.02) and enhanced self-confidence (p < 0.03). Results indicate a direct action of prolonged intranasal administration of insulin on brain functions, improving memory and mood in the absence of systemic side effects. These findings could be of relevance for the treatment of patients with memory disorders like in Alzheimer's disease.
先前的研究表明胰岛素对记忆功能有急性改善作用。为了研究与人类大脑胰岛素活性长期增加相关的记忆变化,我们在此采用鼻内给药途径,已知该途径能使药物直接进入脑脊液腔室。基于先前的结果表明胰岛素受体在边缘和海马区域普遍存在,以及全身注射胰岛素可改善记忆,我们预期鼻内注射胰岛素主要能改善依赖海马体的陈述性记忆功能。此外,预期情绪也会有所改善。我们在38名健康受试者(24名男性)中进行了双盲、受试者间比较,研究了8周鼻内注射胰岛素(人常规胰岛素4×40 IU/天)对陈述性记忆(单词列表的即时和延迟回忆)、注意力(斯特鲁普测试)和情绪的影响。安慰剂组和胰岛素组的血糖和血浆胰岛素水平没有差异。鼻内注射胰岛素8周后,单词的延迟回忆显著改善(回忆的单词数,安慰剂组2.92±1.00,胰岛素组6.20±1.03,p<0.05)。此外,注射胰岛素后的受试者报告情绪有所改善,如愤怒减少(p<0.02)和自信心增强(p<0.03)。结果表明长期鼻内注射胰岛素对脑功能有直接作用,在无全身副作用的情况下改善记忆和情绪。这些发现可能与治疗阿尔茨海默病等记忆障碍患者有关。