Baartman Tamzyn L, Swanepoel Tanya, Barrientos Ruth M, Laburn Helen P, Mitchell Duncan, Harden Lois M
Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, South Africa.
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA.
Behav Brain Res. 2017 May 1;324:155-163. doi: 10.1016/j.bbr.2017.02.020. Epub 2017 Feb 14.
The influence of brain interleukin-1 (IL-1ß) on memory processes includes both detrimental and beneficial effects. To further explore the dynamics of brain IL-1ß in mediating learning and memory during acute sickness, we injected species-homologous rat IL-1ß (100ng/5μl) or vehicle (0.1% bovine serum albumin, 5μl) directly into the cisterna magna (i.c.m.) of male Sprague-Dawley rats. We measured, in parallel, body temperature, food intake, body mass, cage activity, as well as learning and memory using contextual fear conditioning. To investigate the effects of IL-1ß on learning and memory processes we used: (1) a retrograde experiment that involved injecting rats i.c.m. with IL-1ß immediately after training in the novel context, and (2) an anterograde experiment that involved injecting rats i.c.m. with IL-1ß two hours before training in the novel context. In addition, hypothalamic and hippocampal concentrations of IL-1β were measured at several time points following injection. Administration of IL-1ß induced fever, lethargy and anorexia for∼two-to-three days and increased the concentration of IL-1ß in the hippocampus and hypothalamus for at least eight hours. Training in the context immediately before IL-1ß administration (retrograde experiment), did not impair contextual and auditory fear memory. However, when training in the context occurred concurrently with elevated hippocampal IL-1ß levels, two hours after IL-1ß administration (anterograde experiment), contextual, but not auditory, fear memory was impaired. Our results show that there are instances where memory consolidation can occur concurrently with elevated levels of IL-1ß in the hippocampus, fever, anorexia and lethargy during acute short-term sickness.
脑内白细胞介素-1（IL-1β）对记忆过程的影响既有有害的一面，也有有益的一面。为了进一步探究急性疾病期间脑内IL-1β在介导学习和记忆过程中的动态变化，我们将同种大鼠IL-1β（100ng/5μl）或溶剂（0.1%牛血清白蛋白，5μl）直接注射到雄性Sprague-Dawley大鼠的脑大池（i.c.m.）中。同时，我们测量了体温、食物摄入量、体重、笼内活动，以及使用情境恐惧条件反射来评估学习和记忆。为了研究IL-1β对学习和记忆过程的影响，我们采用了：（1）逆行实验，即在新环境中训练后立即给大鼠脑内注射IL-1β；（2）顺行实验，即在新环境中训练前两小时给大鼠脑内注射IL-1β。此外，在注射后的几个时间点测量下丘脑和海马中IL-1β的浓度。注射IL-1β会引起约两到三天的发热、嗜睡和厌食，并使海马和下丘脑中IL-1β的浓度至少升高八小时。在注射IL-1β之前立即在该环境中进行训练（逆行实验），不会损害情境和听觉恐惧记忆。然而，当在注射IL-1β两小时后，在海马IL-1β水平升高的同时在该环境中进行训练（顺行实验），情境恐惧记忆受损，但听觉恐惧记忆未受损。我们的结果表明，在急性短期疾病期间海马中IL-1β水平升高、发热、厌食和嗜睡的情况下，记忆巩固仍有可能同时发生。
