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

Lee, Kyung Jin; Shim, Insop; Sung, Jae Hoon; Hong, Jae Taek; Kim, Il Sup; Cho, Chul Bum

doi:10.3340/jkns.2016.0202.020

Cited by 10 publications

(5 citation statements)

References 27 publications

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“…EPN stimulation increased striatal glutamate levels in NL with DBS category and 6-HD with DBS category compared to NL category and 6-HD category, respectively. This result is in accordance with findings of other reports about increased striatal glutamate levels after STN stimulation [ 9 , 11 , 15 ]. Such same results of increased striatal glutamate in both STN and EPN stimulation cannot be explained by the same mechanism of STN and EPN stimulation.…”

Section: Discussionsupporting

confidence: 94%

Change of Extracellular Glutamate Level in Striatum during Deep Brain Stimulation of the Entopeduncular Nucleus in Rats

Lee

Sung

Hong

et al. 2019

J Korean Neurosurg Soc

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ObjectiveGlobus pallidus interna (GPi) is acknowledged as an essential treatment for advanced Parkinson’s disease (PD). Nonetheless, the neurotransmitter study about its results is undiscovered. The goal of this research was to examine influences of entopeduncular nucleus (EPN) stimulation, identical to human GPi, in no-lesioned (NL) rat and 6-hydroxydopamine (6-HD)-lesioned rat on glutamate change in the striatum. MethodsExtracellular glutamate level changes in striatum of NL category, NL with deep brain stimulation (DBS) category, 6-HD category, and 6-HD with DBS category were examined using microdialysis and high-pressure liquid chromatography. Tyrosine hydroxylase (TH) immunoreactivities in substantia nigra and striatum of the four categories were also analyzed. ResultsExtracellular glutamate levels in the striatum of NL with DBS category and 6-HD with DBS category were significantly increased by EPN stimulation compared to those in the NL category and 6-HD category. EPN stimulation had no significant effect on the expression of TH in NL or 6-HD category. ConclusionClinical results of GPi DBS are not only limited to direct inhibitory outflow to thalamus. They also include extensive alteration within basal ganglia.

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Section: Discussionsupporting

confidence: 94%

Change of Extracellular Glutamate Level in Striatum during Deep Brain Stimulation of the Entopeduncular Nucleus in Rats

Lee

Sung

Hong

et al. 2019

J Korean Neurosurg Soc

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“…However, we observed stable glutamate release during and after the first and fifth DBS sessions, which were below the levels observed in PD-induced animals. Interestingly, it has been shown that acute, high-frequency stimulation (as applied in DBS) induces astrocyte-mediated glutamatergic release in vitro [ 70 ], as glutamate release was observed after 20 min of STN-DBS in hemiparkinsonian rats [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Subthalamic Stimulation and Electrode Implantation in the Striatal Microenvironment in a Parkinson’s Disease Rat Model

Campos

Martinez

Auada

et al. 2022

IJMS

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Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is considered the gold-standard treatment for PD; however, underlying therapeutic mechanisms need to be comprehensively elucidated, especially in relation to glial cells. We aimed to understand the effects of STN-microlesions and STN-DBS on striatal glial cells, inflammation, and extracellular glutamate/GABAergic concentration in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Rats with unilateral striatal 6-OHDA and electrodes implanted in the STN were divided into two groups: DBS OFF and DBS ON (5 days/2 h/day). Saline and 6-OHDA animals were used as control. Akinesia, striatal reactivity for astrocytes, microglia, and inflammasome, and expression of cytokines, cell signaling, and excitatory amino acid transporter (EAAT)-2 were examined. Moreover, striatal microdialysis was performed to evaluate glutamate and GABA concentrations. The PD rat model exhibited akinesia, increased inflammation, glutamate release, and decreased glutamatergic clearance in the striatum. STN-DBS (DBS ON) completely abolished akinesia. Both STN-microlesion and STN-DBS decreased striatal cytokine expression and the relative concentration of extracellular glutamate. However, STN-DBS inhibited morphological changes in astrocytes, decreased inflammasome reactivity, and increased EAAT2 expression in the striatum. Collectively, these findings suggest that the beneficial effects of DBS are mediated by a combination of stimulation and local microlesions, both involving the inhibition of glial cell activation, neuroinflammation, and glutamate excitotoxicity.

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“…Normal levels of GABA help to maintain the tightness and function of the blood-brain barrier [38]. Animal experiments have shown that the levels of GABA in the striatum of PD model are decreased, while highfrequency stimulation can signi cantly increase the levels of GABA in the striatum [39]. Clinical studies have found reduced levels of GABA are associated with visual hallucinations in PD [40].…”

Section: Discussionmentioning

confidence: 99%

Metagenomic analysis of gut microbiota in Parkinson's disease patients from Central China

Zhang

Zhao

Fang

et al. 2020

Preprint

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Background: Parkinson's disease (PD) is one of the most common neurodegenerative diseases, pathologic and epidemiologic studies suggest that gut microbiota may play important roles in the occurrence and progression of Parkinson's disease. However, the alterations in fecal microbiome in PD patients from Central China has not been investigated. Therefore, in this case-control study, we characterised the gut microbial community of 46 PD patients and compared it to those of healthy spouses by using metagenomic shotgun sequencing. Correlation between altered microbiota and clinical features were examined, functional pathways of gut microbiota were estimated, and potential biomarker were explored for further understaning of gut microbiota in PD. Results: Microbial communities in the feces of PD patients were notably different from those of healthy spouses at species level. Gut microbiota of patients was characterized by depletion of Prevotella_copri and Bacteroides_fragilis, while the Bacteroides_stercoris and Escherichia_coli were markedly elevated. Correlation analysis found that most identified species were negatively correlated with disease clinical features. In particular, Prevotella_copri was negatively correlated with age and UPDRS Ⅲ score. Random forest model indicated that 6 species including Prevotella_copri had good predictive value for disease. Functional analyses of the metagenomes revealed differences in microbiota metabolism. Pathways associated with superpathway of thiamin diphosphate biosynthesis, 4-aminobutanoate degradation, glucose-1-phosphate degradation and methylphosphonate degradation were significant increase in patients, while pathways associated with aromatic amino acid biosynthesis, chorismate biosynthesis, thiamin formation and pyrimidine deoxyribonucleosides salvage were significantly decrease. Functional pathways of Prevotella_copri were mainly concentrated in UMP biosynthesis, S-adenosyl-L-methionine cycle and guanosine ribonucleotides de novo biosynthesis. Conclusion: Our findings confirmed changes of gut microbiota in Chinese patients with PD. Altered microbiota had correlation with the clinical characteristics of disease, which may used as potential biomarkers. Different functional pathways of gut microbiota in PD patients will help to improve our understanding of the mechanism in disease, and targeting on gut microbiota may be one of the new therapeutic choices of PD in the future.

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

Cited by 10 publications

References 27 publications

Change of Extracellular Glutamate Level in Striatum during Deep Brain Stimulation of the Entopeduncular Nucleus in Rats

Change of Extracellular Glutamate Level in Striatum during Deep Brain Stimulation of the Entopeduncular Nucleus in Rats

Effect of Subthalamic Stimulation and Electrode Implantation in the Striatal Microenvironment in a Parkinson’s Disease Rat Model

Metagenomic analysis of gut microbiota in Parkinson's disease patients from Central China

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