Gastrodin ameliorates Parkinson's disease by downregulating connexin 43

Wang,Yu; Wu,Zhe; Liu,Xu; Fu,Qunying

doi:10.3892/mmr.2013.1535

Gastrodin ameliorates Parkinson's disease by downregulating connexin 43

Authors:
- Yu Wang
- Zhe Wu
- Xu Liu
- Qunying Fu
View Affiliations

Affiliations: Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: June 19, 2013 https://doi.org/10.3892/mmr.2013.1535
Pages: 585-590

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Gastrodin, the predominant constituent of a Chinese herbal medicine, has been utilized in the prevention of Parkinson's disease (PD); however, its mechanism of action remains unknown. Astrocytes are involved in PD and are proposed to be coupled with gap junction connexin 43 (Cx43). To evaluate the effects of gastrodin on PD, the effect of gastrodin on Cx43 in astrocytes and in a PD model were observed. Different doses of gastrodin were added to the astrocyte culture medium or injected into the rotenone model of PD. The relative expression of Cx43 was determined by qPCR and western blot analysis, while gap junctional intercellular communication (GJIC) was quantified using fluorescence recovery after photobleaching (FRAP). The phosphorylated Cx43 was significantly inhibited by gastrodin and the quantity of GJIC was significantly downregulated compared with that of the control cells (P<0.05). In addition, in the rat model of PD induced by rotenone, phosphorylated Cx43 was selectively enhanced in the striatal and hippocampal regions. The enhanced activity was inhibited significantly by gastrodin treatment (P<0.01). Gastrodin results in the prevention of PD by reducing the expression of Cx43 and inhibiting the phosphorylation of Cx43; therefore, it may offer a potential therapeutic alternative for patients with PD.

View Figures

View References

1	Paisán-Ruíz C, Jain S, Evans EW, et al: Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron. 44:595–600. 2004.PubMed/NCBI
2	Zhang X, Lu L, Liu S, Ye W, Wu J and Zhang X: Acetylcholinesterase deficiency decreases apoptosis in dopaminergic neurons in the neurotoxin model of Parkinson’s disease. Int J Biochem Cell Biol. 45:265–272. 2013.PubMed/NCBI
3	Salama M, Ellaithy A, Helmy B, et al: Colchicine protects dopaminergic neurons in a rat model of Parkinson’s disease. CNS Neurol Disord Drug Targets. 11:836–843. 2012.PubMed/NCBI
4	Ahn EH, Kim DW, Shin MJ, et al: PEP-1-ribosomal protein S3 protects dopaminergic neurons in an MPTP-induced Parkinson’s disease mouse model. Free Radic Biol Med. 55:36–45. 2013.PubMed/NCBI
5	Tönges L, Frank T, Tatenhorst L, et al: Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson’s disease. Brain. 135:3355–3370. 2012.PubMed/NCBI
6	Ali F, Stott SR and Barker RA: Stem cells and the treatment of Parkinson’s disease. Exp Neurol. Jan 6–2013.(Epub ahead of print).
7	Nishimura K and Takahashi J: Therapeutic application of stem cell technology toward the treatment of Parkinson’s disease. Biol Pharm Bull. 36:171–175. 2013.
8	Kim H: Neuroprotective herbs for stroke therapy in traditional eastern medicine. Neurol Res. 27:287–301. 2005. View Article : Google Scholar : PubMed/NCBI
9	Pearl PL, Drillings IM and Conry JA: Herbs in epilepsy: evidence for efficacy, toxicity, and interactions. Semin Pediatr Neurol. 18:203–208. 2011. View Article : Google Scholar : PubMed/NCBI
10	Schachter SC: Botanicals and herbs: a traditional approach to treating epilepsy. Neurotherapeutics. 6:415–420. 2009. View Article : Google Scholar : PubMed/NCBI
11	Manavalan A, Ramachandran U, Sundaramurthi H, et al: Gastrodia elata Blume (tianma) mobilizes neuro-protective capacities. Int J Biochem Mol Biol. 3:219–241. 2012.PubMed/NCBI
12	Li C, Chen X, Zhang N, Song Y and Mu Y: Gastrodin inhibits neuroinflammation in rotenone-induced Parkinson’s disease model rats. Neural Regen Res. 7:325–331. 2012.(In Chinese).
13	Karuppagounder SS, Madathil KS, Pandey M, Haobam R, Rajamma U and Mohanakumar KP: Quercetin up-regulates mitochondrial complex-I activity to protect against programmed cell death in rotenone model of Parkinson’s disease in rats. Neuroscience. 236:136–148. 2013.PubMed/NCBI
14	Xiong N, Long X, Xiong J, et al: Mitochondrial complex I inhibitor rotenone-induced toxicity and its potential mechanisms in Parkinson’s disease models. Crit Rev Toxicol. 42:613–632. 2012.
15	Drinkut A, Tereshchenko Y, Schulz JB, Bähr M and Kügler S: Efficient gene therapy for Parkinson’s disease using astrocytes as hosts for localized neurotrophic factor delivery. Mol Ther. 20:534–543. 2012.
16	Hauser DN and Cookson MR: Astrocytes in Parkinson’s disease and DJ-1. J Neurochem. 117:357–358. 2011.
17	Rappold PM and Tieu K: Astrocytes and therapeutics for Parkinson’s disease. Neurotherapeutics. 7:413–423. 2010.
18	Rouach N and Giaume C: Connexins and gap junctional communication in astrocytes are targets for neuroglial interaction. Prog Brain Res. 132:203–214. 2001. View Article : Google Scholar : PubMed/NCBI
19	Dermietzel R, Gao Y, Scemes E, et al: Connexin43 null mice reveal that astrocytes express multiple connexins. Brain Res Brain Res Rev. 32:45–56. 2000. View Article : Google Scholar : PubMed/NCBI
20	Nagy JI and Rash JE: Connexins and gap junctions of astrocytes and oligodendrocytes in the CNS. Brain Res Brain Res Rev. 32:29–44. 2000. View Article : Google Scholar : PubMed/NCBI
21	Thompson RJ and Macvicar BA: Connexin and pannexin hemichannels of neurons and astrocytes. Channels (Austin). 2:81–86. 2008. View Article : Google Scholar : PubMed/NCBI
22	Li X and Simard JM: Multiple connexins form gap junction channels in rat basilar artery smooth muscle cells. Circ Res. 84:1277–1284. 1999. View Article : Google Scholar : PubMed/NCBI
23	Kawasaki A, Hayashi T, Nakachi K, et al: Modulation of connexin 43 in rotenone-induced model of Parkinson’s disease. Neuroscience. 160:61–68. 2009.PubMed/NCBI
24	Ya-qin C, Yi-fan S, Hong C, Jian-ping W and Jiao D: Effects of gastrodin on Cx43 expression in temporal lobe cortex and hippocampus of pentylenetetrazole-induced epileptic immature rats. Journal of Lanzhou University (Medical Sciences). 34:92008.
25	Mulcahy P, O’Doherty A, Paucard A, O’Brien T, Kirik D and Dowd E: The behavioural and neuropathological impact of intranigral AAV-α-synuclein is exacerbated by systemic infusion of the Parkinson’s disease-associated pesticide, rotenone, in rats. Behav Brain Res. 243:6–15. 2013.PubMed/NCBI
26	Thakur P and Nehru B: Anti-inflammatory properties rather than anti-oxidant capability is the major mechanism of neuroprotection by sodium salicylate in a chronic rotenone model of Parkinson’s disease. Neuroscience. 231:420–431. 2013.PubMed/NCBI
27	Care IoLARCo, Animals UoL and Resources NIoHDoR. Guide for the care and use of laboratory animals. US Department of Health and Human Services, Public Health Service, National Insititutes of Health; 1985
28	Wisniewska-Kruk J, Hoeben KA, Vogels IM, et al: A novel co-culture model of the blood-retinal barrier based on primary retinal endothelial cells, pericytes and astrocytes. Exp Eye Res. 96:181–190. 2012. View Article : Google Scholar : PubMed/NCBI
29	Takizawa T, Gudla PR, Guo L, Lockett S and Misteli T: Allele-specific nuclear positioning of the monoallelically expressed astrocyte marker GFAP. Genes Dev. 22:489–498. 2008. View Article : Google Scholar : PubMed/NCBI
30	Kruger NJ: The Bradford method for protein quantitation. Methods Mol Biol. 32:9–15. 1994.PubMed/NCBI
31	Chen VC, Gouw JW, Naus CC and Foster LJ: Connexin multi-site phosphorylation: mass spectrometry-based proteomics fills the gap. Biochim Biophys Acta. 1828:23–34. 2013. View Article : Google Scholar : PubMed/NCBI
32	Jongen WM, Fitzgerald DJ, Asamoto M, et al: Regulation of connexin 43-mediated gap junctional intercellular communication by Ca²⁺ in mouse epidermal cells is controlled by E-cadherin. J Cell Biol. 114:545–555. 1991. View Article : Google Scholar : PubMed/NCBI
33	Baucum AJ II, Brown AM and Colbran RJ: Differential association of postsynaptic signaling protein complexes in striatum and hippocampus. J Neurochem. 124:490–501. 2013. View Article : Google Scholar : PubMed/NCBI
34	Fidalgo C, Conejo NM, González-Pardo H and Arias JL: Functional interaction between the dorsal hippocampus and the striatum in visual discrimination learning. J Neurosci Res. 90:715–720. 2012. View Article : Google Scholar : PubMed/NCBI
35	Xu X, Lu Y and Bie X: Protective effects of gastrodin on hypoxia-induced toxicity in primary cultures of rat cortical neurons. Planta Med. 73:650–654. 2007. View Article : Google Scholar : PubMed/NCBI
36	Levine AJ, Harris CR and Puzio-Kuter AM: The interfaces between signal transduction pathways: IGF-1/mTor, p53 and the Parkinson Disease pathway. Oncotarget. 3:1301–1307. 2012.PubMed/NCBI