Goodfellow Molly J, Shin Youn Ju, Lindquist Derick H
Department of Psychology, The Ohio State University, 1835 Neil Ave., Columbus, OH 43210, USA.
Department of Neuroscience, The Ohio State University, 1835 Neil Ave., Columbus, OH 43210, USA.
Behav Brain Res. 2018 Feb 15;338:28-31. doi: 10.1016/j.bbr.2017.09.047. Epub 2017 Oct 5.
Impairments in behavior and cognition are common in individuals diagnosed with fetal alcohol spectrum disorders (FASD). In this study, FASD model rats were intragastrically intubated with ethanol (5g/kg/day; 5E), sham-intubated (SI), or maintained as naïve controls (NC) over postnatal days (PD) 4-9. Ethanol exposure during this human third trimester-equivalent period induces persistent impairments in hippocampus-dependent learning and memory. The ability of ibuprofen (IBU), a non-steroidal anti-inflammatory drug, to diminish ethanol-induced neuroinflammation and rescue deficits in hippocampus-dependent trace fear conditioning (TFC) was investigated in 5E rats. Phosphate buffered saline vehicle (VEH) or IBU was injected 2h following ethanol exposure over PD4-9, followed by quantification of inflammation-related genes in the dorsal hippocampus of PD10 rats. The 5E-VEH rats exhibited significant increases in Il1b and Tnf, but not Itgam or Gfap, relative to NC, SI-VEH, and 5E-IBU rats. In separate groups of PD31-33 rats, conditioned fear (freezing) was significantly reduced in 5E-VEH rats during TFC testing, but not acquisition, compared to SI-VEH and, critically, 5E-IBU rats. Results suggest neuroimmune activation in response to ethanol within the neonate hippocampus contributes to later-life cognitive dysfunction.
行为和认知障碍在被诊断患有胎儿酒精谱系障碍（FASD）的个体中很常见。在本研究中，FASD模型大鼠在出生后第4至9天通过胃管灌胃给予乙醇（5g/kg/天；5E）、假灌胃（SI）或作为未处理对照（NC）饲养。在这个相当于人类妊娠晚期的时期暴露于乙醇会导致海马体依赖性学习和记忆的持续损伤。研究了非甾体抗炎药布洛芬（IBU）减轻乙醇诱导的神经炎症并挽救5E大鼠海马体依赖性痕迹恐惧条件反射（TFC）缺陷的能力。在出生后第4至9天乙醇暴露后2小时注射磷酸盐缓冲盐水载体（VEH）或IBU，随后对出生后第10天大鼠背侧海马体中炎症相关基因进行定量分析。与NC、SI-VEH和5E-IBU大鼠相比，5E-VEH大鼠的Il1b和Tnf显著增加，但Itgam或Gfap没有增加。在出生后第31至33天的单独几组大鼠中，与SI-VEH以及至关重要的5E-IBU大鼠相比，5E-VEH大鼠在TFC测试期间的条件性恐惧（僵住）显著降低，但在习得阶段没有降低。结果表明，新生儿海马体对乙醇的神经免疫激活会导致后期的认知功能障碍。
