Prenatal Cannabinoid Exposure Elicits Memory Deficits Associated with Reduced PSA-NCAM Expression, Altered Glutamatergic Signaling, and Adaptations in Hippocampal Synaptic Plasticity.
Prenatal Cannabinoid Exposure Elicits Memory Deficits Associated with Reduced PSA-NCAM Expression, Altered Glutamatergic Signaling, and Adaptations in Hippocampal Synaptic Plasticity.
复制标题
产前大麻素暴露会引起与降低的PSA-NCAM表达，改变谷氨酸能信号传导以及海马突触可塑性适应相关的记忆缺陷。
作者：
大麻现在是孕妇中最常使用的非法物质之一。这尤其令人担忧，因为在发育过程中接触大麻素会引起持久的神经功能和认知改变。本研究调查了产前大麻素暴露（PCE）导致青少年后代学习和记忆缺陷的机制。给怀孕大鼠施用合成大麻素激动剂WIN55,212 - 2，并进行了一系列行为、电生理和免疫化学研究，以确定青少年后代记忆缺陷的潜在机制。青少年PCE动物的海马依赖性记忆缺陷与海马谢弗侧支 - CA1突触处的长时程增强（LTP）降低和长时程抑制（LTD）增强以及GluN2A和GluN2B介导的信号传导之间的失衡有关。此外，PCE降低了神经细胞黏附分子（NCAM）和多聚唾液酸化 - NCAM（PSA - NCAM）的基因和蛋白质表达，这对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，表明PSA介导的GluN2A和GluN2B信号通路的改变可能是PCE导致海马突触可塑性受损的原因。这些发现增进了我们目前对PCE如何影响记忆以及如何为未来的治疗目的操纵这一过程的理解。
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.
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影响因子：
7.7
作者：
Balmer TS;Borges-Merjane C;Trussell LO
通讯作者：
Trussell LO
影响因子：
5.4
作者：
Castelli V;Lavanco G;Feo S;D'Amico C;Micale V;Kuchar M;Plescia F;Brancato A;Cannizzaro C
通讯作者：
Cannizzaro C
影响因子：
3.2
作者：
Alhowail, Ahmad H.;Bloemer, Jenna;Suppiramaniam, Vishnu
通讯作者：
Suppiramaniam, Vishnu
影响因子：
3.3
作者：
Antonelli, T;Tanganelli, S;Ferraro, L
通讯作者：
Ferraro, L
影响因子：
2.4
作者：
Li, Rui;Huang, Fen-Sheng;Abbas, Abdul-Karim;Wigstroem, Holger
通讯作者：
Wigstroem, Holger