PDF(Pubmed)
Abstract：
Cannabis is now one of the most commonly used illicit substances among pregnant women. This is particularly concerning since developmental exposure to cannabinoids can elicit enduring neurofunctional and cognitive alterations. This study investigates the mechanisms of learning and memory deficits resulting from prenatal cannabinoid exposure (PCE) in adolescent offspring. The synthetic cannabinoid agonist WIN55,212-2 was administered to pregnant rats, and a series of behavioral, electrophysiological, and immunochemical studies were performed to identify potential mechanisms of memory deficits in the adolescent offspring. Hippocampal-dependent memory deficits in adolescent PCE animals were associated with decreased long-term potentiation (LTP) and enhanced long-term depression (LTD) at hippocampal Schaffer collateral-CA1 synapses, as well as an imbalance between GluN2A- and GluN2B-mediated signaling. Moreover, PCE reduced gene and protein expression of neural cell adhesion molecule (NCAM) and polysialylated-NCAM (PSA-NCAM), which are critical for GluN2A and GluN2B signaling balance. Administration of exogenous PSA abrogated the LTP deficits observed in PCE animals, suggesting PSA mediated alterations in GluN2A- and GluN2B- signaling pathways may be responsible for the impaired hippocampal synaptic plasticity resulting from PCE. These findings enhance our current understanding of how PCE affects memory and how this process can be manipulated for future therapeutic purposes.
摘要：
大麻现在是孕妇中最常用的非法物质之一。这尤其令人担忧，因为发育中暴露于大麻素可以引起持久的神经功能和认知改变。这项研究调查了青春期后代产前大麻素暴露（PCE）导致的学习和记忆缺陷的机制。将合成大麻素激动剂WIN55,212-2施用于怀孕大鼠，和一系列的行为，电生理学,并进行了免疫化学研究，以确定青春期后代记忆缺陷的潜在机制。青春期PCE动物的海马依赖性记忆缺陷与海马Schaffer侧支CA1突触的长期增强（LTP）降低和长期抑郁（LTD）增强有关，以及GluN2A-和GluN2B-介导的信号之间的不平衡。此外，PCE降低神经细胞粘附分子（NCAM）和多唾液酸化NCAM（PSA-NCAM）的基因和蛋白质表达，这对于GluN2A和GluN2B信号平衡至关重要。外源性PSA的施用消除了在PCE动物中观察到的LTP缺陷，提示PSA介导的GluN2A-和GluN2B-信号通路的改变可能是PCE导致的海马突触可塑性受损的原因。这些发现增强了我们目前对PCE如何影响记忆以及如何为将来的治疗目的操纵该过程的理解。
