Prenatal Exposure to Δ9-Tetrahydrocannabinol Affects Hippocampus-Related Cognitive Functions in the Adolescent Rat Offspring: Focus on Specific Markers of Neuroplasticity.
Prenatal Exposure to Δ9-Tetrahydrocannabinol Affects Hippocampus-Related Cognitive Functions in the Adolescent Rat Offspring: Focus on Specific Markers of Neuroplasticity.
复制标题
DOI：
10.3390/pharmaceutics15020692
复制
发表时间：
2023-02-17
期刊：
影响因子：
5.4
通讯作者：
Cannizzaro C
中科院分区：
文献类型：
--
作者：
Castelli V;Lavanco G;Feo S;D'Amico C;Micale V;Kuchar M;Plescia F;Brancato A;Cannizzaro C
先前的证据表明，产前接触四氢大麻酚（pTHC）会使神经发育轨迹偏离正常，导致情绪调节受损和边缘记忆的易损表型。在此，我们旨在研究pTHC对青春期雄性子代海马相关认知功能和神经可塑性标志物的影响。从妊娠第5天到第20天，Wistar大鼠接触四氢大麻酚（2mg/kg），并在强化动机的Can测试和厌恶驱动的Barnes迷宫测试中进行空间记忆、物体识别记忆和反转学习测试；在旷场、高架十字迷宫和蔗糖偏好测试中分别评估其运动活动和探索行为、类焦虑行为以及对自然奖赏的反应。在海马中测量N - 甲基 - D - 天冬氨酸（NMDA）NR1 - 2A亚基、代谢型谷氨酸受体5（mGluR5）及其各自的支架蛋白PSD95和Homer1，以及大麻素受体1（CB1R）和神经调节蛋白HINT1的基因表达水平。pTHC子代在空间和物体识别记忆以及反转学习方面表现出缺陷，运动活动增加，NR1表达增加，NR2A和PSD95表达降低，mGluR5和Homer1表达增加，CB1R和HINT1海马mRNA水平升高。我们的数据表明，pTHC与空间认知加工的特定损伤以及海马神经可塑性的效应因子有关，并为未来的药理学挑战提出了新的靶点。
Previous evidence suggests that prenatal exposure to THC (pTHC) derails the neurodevelopmental trajectories towards a vulnerable phenotype for impaired emotional regulation and limbic memory. Here we aimed to investigate pTHC effect on hippocampus-related cognitive functions and markers of neuroplasticity in adolescent male offspring. Wistar rats were exposed to THC (2 mg/kg) from gestational day 5 to 20 and tested for spatial memory, object recognition memory and reversal learning in the reinforce-motivated Can test and in the aversion-driven Barnes maze test; locomotor activity and exploration, anxiety-like behaviour, and response to natural reward were assessed in the open field, elevated plus maze, and sucrose preference tests, respectively. The gene expression levels of NMDA NR1-2A subunits, mGluR5, and their respective scaffold proteins PSD95 and Homer1, as well as CB1R and the neuromodulatory protein HINT1, were measured in the hippocampus. pTHC offspring exhibited deficits in spatial and object recognition memory and reversal learning, increased locomotor activity, increased NR1-, decreased NR2A- and PSD95-, increased mGluR5- and Homer1-, and augmented CB1R- and HINT1-hippocampal mRNA levels. Our data shows that pTHC is associated with specific impairment in spatial cognitive processing and effectors of hippocampal neuroplasticity and suggests novel targets for future pharmacological challenges.
登录
查看更多内容
影响因子：
4.7
作者：
Brancato A;Castelli V;Lavanco G;Tringali G;Micale V;Kuchar M;D'Amico C;Pizzolanti G;Feo S;Cannizzaro C
通讯作者：
Cannizzaro C
影响因子：
4.7
作者：
Castaldo, Pasqualina;Magi, Simona;Cuomo, Vincenzo
通讯作者：
Cuomo, Vincenzo
影响因子：
--
作者：
Busquets Garcia, Arnau;Soria-Gomez, Edgar;Marsicano, Giovanni
通讯作者：
Marsicano, Giovanni
影响因子：
3.3
作者：
Antonelli, T;Tanganelli, S;Ferraro, L
通讯作者：
Ferraro, L
影响因子：
8.8
作者：
da Cruz, Jose F. Oliveira;Busquets-Garcia, Arnau;Soria-Gomez, Edgar
通讯作者：
Soria-Gomez, Edgar