PMID- 30816461 OWN - NLM STAT- MEDLINE DCOM- 20190730 LR - 20200309 IS - 1791-3004 (Electronic) IS - 1791-2997 (Print) IS - 1791-2997 (Linking) VI - 19 IP - 4 DP - 2019 Apr TI - Early intervention with gastrodin reduces striatal neurotoxicity in adult rats with experimentally‑induced diabetes mellitus. PG - 3114-3122 LID - 10.3892/mmr.2019.9954 [doi] AB - Glutamate‑induced excitotoxicity in the striatum has an important role in neurodegenerative diseases. It has been reported that diabetes mellitus (DM) induces excitotoxicity in striatal neurons, although the underlying mechanism remains to be fully elucidated. The present study aimed to investigate the effect of gastrodin on DM‑induced excitotoxicity in the striatal neurons of diabetic rats. Adult Sprague‑Dawley rats were divided into control, diabetic, and gastrodin intervention groups. Diabetes in the rats was induced with a single intraperitoneal injection of streptozotocin (65 mg/kg). In the gastrodin groups, the rats were gavaged with 60 or 120 mg/kg/day gastrodin for 6 weeks, 3 weeks following the induction of diabetes. Pathological alterations in the striatum were assessed using hematoxylin and eosin (H&E) staining. The protein expression levels of phosphorylated (p)‑extracellular signal‑regulated kinase (ERK)1/2, p‑mitogen‑activated protein kinase kinase (MEK)1/2, tyrosine receptor kinase B (TrKB) and brain‑derived neurotrophic factor (BDNF) in the striatal neurons were evaluated by western blotting and double immunofluorescence. Additionally, the extracellular levels of glutamate were measured by microanalysis followed by high‑pressure‑liquid‑chromatography. In diabetic rats, striatal neuronal degeneration was evident following H&E staining, which revealed the common occurrence of pyknotic nuclei. This was coupled with an increase in glutamate levels in the striatal tissues. The protein expression levels of p‑ERK1/2, p‑MEK1/2, TrKB and BDNF in the striatal tissues were significantly increased in the diabetic rats compared with those in the normal rats. In the gastrodin groups, degeneration of the striatal neurons was ameliorated. Furthermore, the expression levels of glutamate, p‑ERK1/2, p‑MEK1/2, TrKB and BDNF in the striatal neurons were decreased. From these findings, it was concluded that reduced neurotoxicity in striatal neurons following treatment with gastrodin may be attributed to its suppressive effects on the expression of p‑ERK1/2, p‑MEK1/2, BDNF and TrKB. FAU - Qi, Yu-Han AU - Qi YH AD - Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China. FAU - Zhu, Rui AU - Zhu R AD - Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China. FAU - Wang, Qing AU - Wang Q AD - Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China. FAU - Li, Qian AU - Li Q AD - Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China. FAU - Liu, Yi-Dan AU - Liu YD AD - Institute of Drug Discovery and Development, Kunming Pharmaceutical Corporation, Kunming, Yunnan 650500, P.R. China. FAU - Qian, Zhong-Yi AU - Qian ZY AD - Department of Morphological Laboratory, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China. FAU - Yang, Zhi-Hong AU - Yang ZH AD - Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China. FAU - Mu, Zhi-Hao AU - Mu ZH AD - Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China. FAU - Liu, Xin-Jie AU - Liu XJ AD - Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China. FAU - Zhang, Mei-Yan AU - Zhang MY AD - Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China. FAU - Wang, Xie AU - Wang X AD - Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China. FAU - Liao, Xin-Yu AU - Liao XY AD - Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China. FAU - Wan, Qi AU - Wan Q AD - Institute of Neuroregeneration and Neurorehabilitation, Department of Neurosurgery of The Affiliated Hospital, Qingdao University, Qingdao, Shandong 266071, P.R. China. FAU - Lu, Di AU - Lu D AD - Biomedical Engineering Research Center, Kunming Medical University, Kunming, Yunnan 650500, P.R. China. FAU - Zou, Ying-Ying AU - Zou YY AD - Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China. LA - eng PT - Journal Article DEP - 20190214 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Benzyl Alcohols) RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Glucosides) RN - 3KX376GY7L (Glutamic Acid) RN - 5YS9U2W3RQ (gastrodin) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) MH - Animals MH - Benzyl Alcohols/*metabolism MH - Biomarkers MH - Brain-Derived Neurotrophic Factor/metabolism MH - Corpus Striatum/*metabolism MH - Diabetes Mellitus, Experimental/*etiology/*metabolism/pathology MH - Gene Expression MH - Glucosides/*metabolism MH - Glutamic Acid/metabolism MH - Male MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Models, Biological MH - Neurons/metabolism MH - Rats MH - Receptor, trkB/metabolism PMC - PMC6423552 EDAT- 2019/03/01 06:00 MHDA- 2019/07/31 06:00 PMCR- 2019/02/14 CRDT- 2019/03/01 06:00 PHST- 2018/06/28 00:00 [received] PHST- 2019/01/11 00:00 [accepted] PHST- 2019/03/01 06:00 [pubmed] PHST- 2019/07/31 06:00 [medline] PHST- 2019/03/01 06:00 [entrez] PHST- 2019/02/14 00:00 [pmc-release] AID - mmr-19-04-3114 [pii] AID - 10.3892/mmr.2019.9954 [doi] PST - ppublish SO - Mol Med Rep. 2019 Apr;19(4):3114-3122. doi: 10.3892/mmr.2019.9954. Epub 2019 Feb 14.