Effects of age, experience and inter-alpha inhibitor proteins on working memory and neuronal plasticity after neonatal hypoxia-ischemia.
Effects of age, experience and inter-alpha inhibitor proteins on working memory and neuronal plasticity after neonatal hypoxia-ischemia.
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DOI：
10.1016/j.bbr.2016.01.016
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发表时间：
2016-04-01
影响因子：
2.7
通讯作者：
Threlkeld SW
中科院分区：
文献类型：
--
作者：
Gaudet CM;Lim YP;Stonestreet BS;Threlkeld SW
新生儿脑缺氧缺血（HI）通常导致认知和感觉障碍。早期的行为经验已被认为可以改善儿童和围产期神经病理学动物模型的认知和感觉结果。与此同时，我们以前表明，治疗免疫调节剂间α抑制蛋白（IAIP）改善新生儿HI损伤大鼠的细胞和行为的结果。本研究的目的是评估早期经验和典型成熟结合IAIP治疗对新生儿HI损伤后空间工作记忆和参考记忆的影响。第二个目的是确定这些变量对海马CA 1神经元形态的影响。受试者被分为两组，暴露于八臂径向水迷宫测试的时间不同：第一组在青少年（早期经验，出生后第36至61天）和成年人（P88 - 113）时进行测试，第二组仅在成年人（P88-113;没有早期经验）时进行测试。每个经验组包括三种处理条件（HI +溶剂、HI + IAIP和假手术受试者）。在三种错误类型（参考记忆（RM）、工作记忆错误（WMC）、工作记忆正确（WMC））中，比较了治疗组和经验组之间的错误手臂输入（错误）。早期经验导致工作记忆表现改善，无论治疗如何。结合IAIPs干预与早期经验提供了一个长期的行为优势，在HI动物的任务的任务的重复组成部分。在解剖学上，早期经验导致IAIP治疗受试者的每个CA 1锥体神经元的基底树突平均数量减少，对照受试者的基底树突长度显著减少，突出了修剪在典型的早期生活学习中的重要性。我们的研究结果支持这一假设，即早期行为经验与IAIP相结合，提高结果的相对要求的认知任务，超越了一个单一的干预策略，并出现促进新生儿脑损伤后的神经元可塑性。
Neonatal cerebral hypoxia-ischemia (HI) commonly results in cognitive and sensory impairments. Early behavioral experience has been suggested to improve cognitive and sensory outcomes in children and animal models with perinatal neuropathology. In parallel, we previously showed that treatment with immunomodulator Inter-alpha Inhibitor Proteins (IAIPs) improves cellular and behavioral outcomes in neonatal HI injured rats. The purpose of the current study was to evaluate the influences of early experience and typical maturation in combination with IAIPs treatment on spatial working and reference memory after neonatal HI injury. A second aim was to determine the effects of these variables on hippocampal CA1 neuronal morphology. Subjects were divided into two groups that differed with respect to the time when exposed to eight arm radial water maze testing: Group one was tested as juveniles (early experience, Postnatal day (P) 36 to 61) and adults (P88 – 113), and Group two was tested in adulthood only (P88-113; without early experience). Three treatment conditions were included in each experience group (HI + Vehicle, HI + IAIPs, and Sham subjects). Incorrect arm entries (errors) were compared between treatment and experience groups across three error types (Reference memory (RM), Working memory incorrect (WMI), Working memory correct (WMC)). Early experience led to improved working memory performance regardless of treatment. Combining IAIPs intervention with early experience provided a long-term behavioral advantage on the WMI component of the task in HI animals. Anatomically, early experience led to a decrease in the average number of basal dendrites per CA1 pyramidal neuron for IAIP treated subjects and a significant reduction in basal dendritic length in control subjects, highlighting the importance of pruning in typical early life learning. Our results support the hypothesis that early behavioral experience combined with IAIPs improve outcome on a relativity demanding cognitive task, beyond that of a single intervention strategy, and appears to facilitate neuronal plasticity following neonatal brain injury.