J Korean Neurosurg Soc.  2017 Feb;60(2):138-145. 10.3340/jkns.2016.0202.020.

Striatal Glutamate and GABA after High Frequency Subthalamic Stimulation in Parkinsonian Rat

Affiliations
  • 1Department of Neurosurgery, Yeoido Saint Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 2Acupuncture & Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University, Seoul, Korea.
  • 3Department of Neurosurgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. medics0919@gmail.com

Abstract


OBJECTIVE
High frequency stimulation (HFS) of the subthalamic nucleus (STN) is recognized as an effective treatment of advanced Parkinson's disease. However, the neurochemical basis of its effects remains unknown. The aim of this study is to investigate the effects of STN HFS in intact and 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rat model on changes of principal neurotransmitters, glutamate, and gamma-aminobutyric acid (GABA) in the striatum.
METHODS
The authors examined extracellular glutamate and GABA change in the striatum on sham group, 6-OHDA group, and 6-OHDA plus deep brain stimulation (DBS) group using microdialysis methods.
RESULTS
High-pressure liquid chromatography was used to quantify glutamate and GABA. The results show that HFS-STN induces a significant increase of extracellular glutamate and GABA in the striatum of 6-OHDA plus DBS group compared with sham and 6-OHDA group.
CONCLUSION
Therefore, the clinical results of STN-HFS are not restricted to the direct STN targets but involve widespread adaptive changes within the basal ganglia.

Keyword

Subthalamic nucleus; Glutamate; GABA; Deep brain stimulation; Parkinson disease

MeSH Terms

Animals
Basal Ganglia
Chromatography, Liquid
Deep Brain Stimulation
gamma-Aminobutyric Acid*
Glutamic Acid*
Microdialysis
Models, Animal
Neurotransmitter Agents
Oxidopamine
Parkinson Disease
Rats*
Subthalamic Nucleus
Glutamic Acid
Neurotransmitter Agents
Oxidopamine
gamma-Aminobutyric Acid

Figure

  • Fig. 1 Apomorphine rotation test. This graph showed that the mean and 95% conÿdence interval in 6-OHDA group (134.3, 114.80 to 153.86) and 6-OHDA plus DBS group (127.66, 101.98 to 153.35). There was no statistical signiÿcance of radiation turns between two groups (p=0.6069). 6-OHDA: 6-hydroxydopamine, DBS: deep brain stimulation.

  • Fig. 2 E°ect of high frequency stimulation of subthalamic nucleus on extracellular glutamate in the striatum measured by microdialysis in rats. Each point represents the mean value±standard error from six rats per group: normal rats without deep brain stimulation (sham group), 6-OHDA-lesioned rats without deep brain stimulation group (6-OHDA group), 6-OHDA-lesioned rats with deep brain stimulation (6-OHDA plus DBS group). 6-OHDA: 6-hydroxydopamine, DBS: deep brain stimulation.

  • Fig. 3 Effect of high frequency stimulation of subthalamic nucleus on extracellular GABA in the striatum measured by microdialysis in rats. Each point represents the mean value±standard error from six rats per group: normal rats without deep brain stimulation (sham group), 6-OHDA-lesioned rats without deep brain stimulation group (6-OHDA group), 6-OHDA-lesioned rats with deep brain stimulation (6-OHDA plus DBS group). GABA: gamma-aminobutyric acid, 6-OHDA: 6-hydroxydopamine, DBS: deep brain stimulation.

  • Fig. 4 Cresyl violet stained photomicrographs showing the sites of deep brain stimulation in the subthalamic nucleus. Scale bar: 250 um. STN: subthalamic nucleus.

  • Fig. 5 Photographs of coronal rat brain sections at nigral and striatal levels. Sham group: tyrosine hydroxylase (TH) immunostaining at nigral and striatal levels has no di°erence between ipsilateral and contralateral side. 6-OHDA group: TH immunostaining at nigra and striatum in ipsilateral side to 6-OHDA lesioned site shows remarkable decrease compared with contralateral side. 6-OHDA plus DBS group: TH immunostaining at nigra and striatum in ipsilateral side to 6-OHDA lesioned site shows mild increase compared with the ipsilateral side in 6-OHDA group. Scale bar=500 um. 6-OHDA: 6-hydroxydopamine, DBS: deep brain stimulation, ST: striatum, SN: substantia nigra, VT: ventral tegmental area.


Cited by  1 articles

Change of Extracellular Glutamate Level in Striatum during Deep Brain Stimulation of the Entopeduncular Nucleus in Rats
Hyun-ju Lee, Jae Hoon Sung, Jae Taek Hong, Il Sup Kim, Seung Ho Yang, Chul Bum Cho
J Korean Neurosurg Soc. 2019;62(2):166-174.    doi: 10.3340/jkns.2018.0122.


Reference

References

1. Abosch A, Kapur S, Lang A, Hussey D, Sime E, Miyasaki J, et al. Stimulation of the subthalamic nucleus in Parkinson’s disease does not produce striatal dopamine release. Neurosurgery. 53:1095–1102. 2003.
Article
2. Bar Gad I, Elias S, Vaadia E, Bergman H. Complex locking rather than complete cessation of neuronal activity in the globus pallidus of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primate in response to pallidal microstimulation. J Neurosci. 24:7410–7419. 2004.
Article
3. Bruet N, Windels F, Carcenac C, Feuerstein C, Bertrand A, Poupard A, et al. Neurochemical mechanisms induced by high frequency stimulation of the subthalamic nucleus: increase of extracellular striatal glutamate and GABA in normal and hemiparkinsonian rats. J Neuropathol Exp Neurol. 62:1228–1240. 2003.
Article
4. Carman LS, Gage FH, Shults CW. Partial lesion of the substantia nigra: relation between extent of lesion and rotational behavior. Brain Res. 553:275–283. 1991.
Article
5. Chevalier G, Deniau JM. Disinhibition as a basic process in the expression of striatal functions. Trends Neurosci. 13:277–280. 1990.
Article
6. DeLong MR. Primate models of movement disorders of basal ganglia origin. Trends Neurosci. 13:281–285. 1990.
Article
7. Deumens R, Blokland A, Prickaerts J. Modeling Parkinson’s disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol. 175:303–317. 2002.
Article
8. Henning J, Koczan D, Glass A, Karopka T, Pahnke J, Rolfs A, et al. Deep brain stimulation in a rat model modulates TH, CaMKIIa and Homer1 gene expression. Eur J Neurosci. 25:239–250. 2007.
Article
9. Hodaie M, Wennberg R, Dostrovsky J, Lozano A. Chronic anterior thalamus stimulation for intractable epilepsy. Epilepsia. 43:603–608. 2002.
Article
10. Krack P, Batir A, Van Blercom Ng, Chabardes S, Fraix Vr, Ardouin C, et al. Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med. 349:1925–1934. 2003.
Article
11. Krack P, Pollak P, Limousin P, Benazzouz A, Benabid AL. Stimulation of subthalamic nucleus alleviates tremor in Parkinson’s disease. Lancet. 350:1675. 1997.
Article
12. Lacombe E, Carcenac C, Boulet S, Feuerstein C, Bertrand A, Poupard A, et al. High-frequency stimulation of the subthalamic nucleus prolongs the increase in striatal dopamine induced by acute l-3,4-dihydroxyphenylalanine in dopaminergic denervated rats. Eur J Neurosci. 26:1670–1680. 2007.
Article
13. Lang AE, Widner H. Deep brain stimulation for Parkinson’s disease: patient selection and evaluation. Mov Disord. 17(Suppl 3):S94–S101. 2002.
Article
14. Limousin P, Pollak P, Benazzouz A, Hoffmann D, Broussolle E, Perret JE, et al. Bilateral subthalamic nucleus stimulation for severe Parkinson’s disease. Mov Disord. 10:672–674. 1995.
Article
15. McIntyre CC, Savasta M, Kerkerian-Le Goff L, Vitek JL. Uncovering the mechanism(s) of action of deep brain stimulation: activation, inhibition, or both. Clin Neurophysiol. 115:1239–1248. 2004.
Article
16. Megías M, Emri Z, Freund TF, Gulyás AI. Total number and distribution of inhibitory and excitatory synapses on hippocampal CA1 pyramidal cells. Neuroscience. 102:527–540. 2001.
Article
17. Meissner W, Harnack D, Reese R, Paul G, Reum T, Ansorge M, et al. High-frequency stimulation of the subthalamic nucleus enhances striatal dopamine release and metabolism in rats. J Neurochem. 85:601–609. 2003.
Article
18. Nambu A. A new approach to understand the pathophysiology of Parkinson’s disease. J Neurol. 252(Suppl 4):IV1–IV4. 2005.
Article
19. Papa SM, Engber TM, Kask AM, Chase TN. Motor fluctuations in levodopa treated parkinsonian rats: relation to lesion extent and treatment duration. Brain Res. 662:69–74. 1994.
Article
20. Paxinos G. The rat nervous system. Amsterdam ; Boston: Elsevier Academic Press;2004.
21. Pollak P, Benabid AL, Gross C, Gao DM, Laurent A, Benazzouz A, et al. Effects of the stimulation of the subthalamic nucleus in Parkinson disease. Rev Neurol (Paris). 149:175–176. 1993.
22. Segovia G, Del Arco A, Mora F. Endogenous glutamate increases extracellular concentrations of dopamine, GABA, and taurine through NMDA and AMPA/kainate receptors in striatum of the freely moving rat: a microdialysis study. J Neurochem. 69:1476–1483. 1997.
Article
23. Shipton EA. Movement disorders and neuromodulation. Neurol Res Int. 2012:309431. 2012.
Article
24. Visser-Vandewalle V, van der Linden C, Temel Y, Celik H, Ackermans L, Spincemaille G, et al. Long-term effects of bilateral subthalamic nucleus stimulation in advanced Parkinson disease: a four year follow-up study. Parkinsonism Relat Disord. 11:157–165. 2005.
Article
25. Wichmann T, Delong MR. Deep-brain stimulation for basal ganglia disorders. Basal Ganglia. 1:65–77. 2011.
Article
26. Wichmann T, DeLong MR, Guridi J, Obeso JA. Milestones in research on the pathophysiology of Parkinson’s disease. Mov Disord. 26:1032–1041. 2011.
Article
27. Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis. Cell. 132:645–660. 2008.
Article
Full Text Links
  • JKNS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr