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在慢性颞下颌关节紊乱模型中,用葡萄(Vitus vinifera)葡萄籽提取物进行膳食补充可防止雌性斯普拉格-道利大鼠三叉神经节中γ-氨基丁酸能蛋白表达受到抑制。

Dietary supplementation with grape seed extract from Vitus vinifera prevents suppression of GABAergic protein expression in female Sprague Dawley trigeminal ganglion in a model of chronic temporomandibular joint disorder.

作者信息

Antonopoulos Sophia R, Garten Daniel A, Durham Paul L

机构信息

Missouri State University, Jordan Valley Innovation Center, Department of Biology, Springfield, MO 65806, USA.

Missouri State University, Jordan Valley Innovation Center, Department of Biology, Springfield, MO 65806, USA.

出版信息

Arch Oral Biol. 2024 Sep;165:106014. doi: 10.1016/j.archoralbio.2024.106014. Epub 2024 May 29.

DOI:10.1016/j.archoralbio.2024.106014
PMID:38833771
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12019862/
Abstract

OBJECTIVE

To investigate cellular changes in protein expression in the trigeminal ganglion in an established preclinical chronic model of temporomandibular joint disorder (TMD) in response to grape seed extract (GSE) supplementation based on its beneficial use in preclinical chronic orofacial pain models.

DESIGN

Three experimental conditions included female Sprague-Dawley rats as naïve controls, and animals subjected to neck muscle inflammation and prolonged jaw opening with and without daily supplementation of GSE in the drinking water prior to inflammation. Changes were evaluated in mechanical sensitivity to von Frey filaments and protein expression in the trigeminal ganglion of animals 14 days post jaw opening.

RESULTS

Calcitonin-gene related peptide and protein kinase A, proteins positively associated with peripheral sensitization and enhanced nociception, did not show elevated expression at day 14 in the model compared to naïve or GSE supplemented animals. However, neuronal levels of glutamate decarboxylase (GAD) 65/67, which are enzymes responsible for the synthesis of the inhibitory neurotransmitter GABA that functions to suppress neuronal excitability, were significantly decreased on day 14 post jaw opening. Similarly, a significant decrease in neuronal expression of the GABA receptor subunits GABAB1 and GABAB2, but not GABAA, was observed in the TMD model. Importantly, GSE prevented suppression of GAD 65/67 and GABAB subunits, maintaining levels similar to naïve animals.

CONCLUSION

Results from our study provide evidence of the downregulation of inhibitory GABAergic proteins in trigeminal ganglion neurons in a preclinical chronic TMD model and the benefits of GSE supplementation in preventing their suppression and maintaining normal levels.

摘要

目的

在已建立的颞下颌关节紊乱病(TMD)临床前慢性模型中,基于葡萄籽提取物(GSE)在临床前慢性口面部疼痛模型中的有益作用,研究三叉神经节中蛋白质表达的细胞变化。

设计

三个实验条件包括雌性Sprague-Dawley大鼠作为未处理的对照,以及在炎症前分别给予和不给予每日饮水中补充GSE的情况下,使动物遭受颈部肌肉炎症和长时间张口的处理。在张口14天后,评估动物对von Frey细丝的机械敏感性以及三叉神经节中的蛋白质表达变化。

结果

与未处理或补充GSE的动物相比,降钙素基因相关肽和蛋白激酶A这两种与外周敏化和痛觉增强呈正相关的蛋白质,在模型中的第14天未显示表达升高。然而,谷氨酸脱羧酶(GAD)65/67的神经元水平,即负责合成抑制性神经递质GABA(其作用是抑制神经元兴奋性)的酶,在张口后第14天显著降低。同样地,在TMD模型中观察到GABA受体亚基GABAB1和GABAB2的神经元表达显著降低,但GABAA未降低。重要的是,GSE可防止GAD 65/67和GABAB亚基受到抑制,使其水平维持在与未处理动物相似的水平。

结论

我们的研究结果提供了证据,表明在临床前慢性TMD模型中,三叉神经节神经元中抑制性GABA能蛋白下调,以及补充GSE在防止其抑制并维持正常水平方面的益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/5b61323a99a1/nihms-2071034-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/5b61a1dd44a1/nihms-2071034-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/710c418a9298/nihms-2071034-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/e1088e3f2d57/nihms-2071034-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/87a4dc6a63ac/nihms-2071034-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/20fe7d2c94ee/nihms-2071034-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/7aa4a36ab465/nihms-2071034-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/61e8e43c3cab/nihms-2071034-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/5b61323a99a1/nihms-2071034-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/5b61a1dd44a1/nihms-2071034-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/710c418a9298/nihms-2071034-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/e1088e3f2d57/nihms-2071034-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/87a4dc6a63ac/nihms-2071034-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/20fe7d2c94ee/nihms-2071034-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/7aa4a36ab465/nihms-2071034-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/61e8e43c3cab/nihms-2071034-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/12019862/5b61323a99a1/nihms-2071034-f0008.jpg

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