Effects of prenatal synthetic cannabinoid exposure on the cerebellum of adolescent rat offspring.
Effects of prenatal synthetic cannabinoid exposure on the cerebellum of adolescent rat offspring.
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DOI：
10.1016/j.heliyon.2021.e06730
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发表时间：
2021-04
期刊：
影响因子：
4
通讯作者：
Dhanasekaran M
中科院分区：
文献类型：
--
作者：
Pinky PD;Majrashi M;Fujihashi A;Bloemer J;Govindarajulu M;Ramesh S;Reed MN;Moore T;Suppiramaniam V;Dhanasekaran M
大麻是全球最常用的非法药物。近期，年轻孕妇使用大麻的情况大幅增加。然而，产前接触大麻素会通过各种机制导致后代出现长期的认知、运动和行为缺陷以及神经回路的改变。尽管这些影响已在海马体中得到研究，但产前接触大麻素对小脑的影响尚未得到很好的阐明。小脑在平衡和运动控制以及诸如注意力、语言和程序性记忆等认知功能方面发挥着重要作用。本研究的目的是调查产前接触大麻素对青春期后代小脑的影响。怀孕大鼠接受合成大麻素激动剂WIN55,212 - 2处理，并对后代的氧化应激、线粒体功能和细胞凋亡的各种小脑标志物进行评估。此外，还检测了与谷氨酸依赖性突触可塑性相关的信号蛋白。孕期给予WIN55,212 - 2通过显著降低氧化应激和亚硝酸盐含量改变了氧化应激标志物。产前接触大麻素后，线粒体复合物I和复合物IV的活性也增强。关于细胞凋亡，pP38水平显著升高，促凋亡因子caspase - 3活性、pERK和pJNK水平显著降低。CB1R和GluA1水平保持不变；然而，GluN2A显著降低。尽管酪氨酸羟化酶活性未改变，但单胺氧化酶活性显著降低。我们的研究表明，产前接触大麻素对小脑的影响与其他脑区相比是独特的，它增强了线粒体功能并促进了神经元存活。需要进一步的研究来评估产前接触大麻素改变小脑过程的机制以及这些改变对行为的影响。
产前接触、大麻素、小脑、线粒体、发育、氧化应激
Cannabis is the most commonly used illicit drug worldwide. Recently, cannabis use among young pregnant women has greatly increased. However, prenatal cannabinoid exposure leads to long-lasting cognitive, motor, and behavioral deficits in the offspring and alterations in neural circuitry through various mechanisms. Although these effects have been studied in the hippocampus, the effects of prenatal cannabinoid exposure on the cerebellum are not well elucidated. The cerebellum plays an important role in balance and motor control, as well as cognitive functions such as attention, language, and procedural memories. The aim of this study was to investigate the effects of prenatal cannabinoid exposure on the cerebellum of adolescent offspring. Pregnant rats were treated with synthetic cannabinoid agonist WIN55,212-2, and the offspring were evaluated for various cerebellar markers of oxidative stress, mitochondrial function, and apoptosis. Additionally, signaling proteins associated with glutamate dependent synaptic plasticity were examined. Administration of WIN55,212-2 during pregnancy altered markers of oxidative stress by significantly reducing oxidative stress and nitrite content. Mitochondrial Complex I and Complex IV activities were also enhanced following prenatal cannabinoid exposure. With regard to apoptosis, pP38 levels were significantly increased, and proapoptotic factor caspase-3 activity, pERK, and pJNK levels were significantly decreased. CB1R and GluA1 levels remained unchanged; however, GluN2A was significantly reduced. There was a significant decrease in MAO activity although tyrosine hydroxylase activity was unaltered. Our study indicates that the effects of prenatal cannabinoid exposure on the cerebellum are unique compared to other brain regions by enhancing mitochondrial function and promoting neuronal survival. Further studies are required to evaluate the mechanisms by which prenatal cannabinoid exposure alters cerebellar processes and the impact of these alterations on behavior. Prenatal exposure, Cannabinoid, Cerebellum, Mitochondria, Developmental, Oxidative stress
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影响因子：
3.1
作者：
Bonnin, A;deMiguel, R;FernandezRuiz, JJ
通讯作者：
FernandezRuiz, JJ
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：
5.3
作者：
Björkblom, B;Östman, N;Coffey, ET
通讯作者：
Coffey, ET
影响因子：
4.8
作者：
Deep, Satya Narayan;Mitra, Sumonto;Poddar, Ranjana
通讯作者：
Poddar, Ranjana
影响因子：
3.8
作者：
BAILEY, JR;CUNNY, HC;SLIKKER, W
通讯作者：
SLIKKER, W