Inhibition of Gap Junction Elevates Glutamate Uptake in Cultured Astrocytes

2018 ◽  
Vol 43 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Katsura Takano ◽  
Masato Ogawa ◽  
Kenji Kawabe ◽  
Mitsuaki Moriyama ◽  
Yoichi Nakamura
Keyword(s):  
Gap Junction ◽  
Glutamate Uptake ◽  
Cultured Astrocytes

scholarly journals Comparison of the Effects of Yokukansan and Yokukansankachimpihange on Glutamate Uptake by Cultured Astrocytes and Glutamate-Induced Excitotoxicity in Cultured PC12 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Zenji Kawakami ◽  
Yuji Omiya ◽  
Kazushige Mizoguchi
Keyword(s):  
Cell Death ◽  
Effective Dose ◽  
Pc12 Cells ◽  
Psychological Symptoms ◽  
Glutamate Uptake ◽  
Inhibitory Effects ◽  
Alternative Formula ◽  
Cultured Astrocytes ◽  
Citrus Unshiu Peel ◽  
Glutamatergic Pathways

The traditional Japanese Kampo medicine yokukansan (YKS) is effective for behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer’s disease. As the pharmacological mechanisms, YKS is known to protect astrocytes from thiamine-deficiency (TD)-induced decreased glutamate (Glu) uptake and neuron model cells (PC 12 cells) from Glu-induced death. Yokukansankachimpihange (YKSCH) is an alternative formula to YKS, in which Citrus unshiu peel and Pinellia tuber are added to the YKS components, and is sometimes used to treat BPSD, but its pharmacological properties remain unknown. This study aims to investigate the cellular pharmacological effects of YKS and YKSCH on glutamatergic pathways, compare their efficacy, and determine the differences and similarities in the activities between these formulations. First, we examined the effects of YKS and YKSCH on Glu uptake by cultured astrocytes under TD conditions. We observed significant ameliorative effects of YKS and YKSCH on the TD-induced decrease in Glu uptake, with a 50% effective dose of 8.9 ± 1.8 μg/mL and 45.3 ± 9.2 μg/mL, respectively. Second, using cultured PC12 cells as a model for neurons, we examined the effects of YKS and YKSCH on Glu-induced cell death. We observed that YKS and YKSCH had significant inhibitory effects on Glu-induced cell death, with a 30% effective dose of 51.4 ± 20.8 μg/mL and 49.2 ± 11.0 μg/mL, respectively. Thus, while YKSCH was less effective than YKS in ameliorating the TD-induced decrease in Glu uptake by astrocytes, the two drugs showed similar inhibitory effects on Glu-induced PC12 cell death. These findings are important for understanding the differences and similarities in pharmacological actions between these drugs.

Adenosine A2A receptors modulate glutamate uptake in cultured astrocytes and gliosomes

Glia ◽  
2012 ◽  
Vol 60 (5) ◽  
pp. 702-716 ◽  
Author(s):  
Marco Matos ◽  
Elisabete Augusto ◽  
Alexandre Dos Santos-Rodrigues ◽  
Michael A. Schwarzschild ◽  
Jiang-Fan Chen ◽  
...  
Keyword(s):  
Glutamate Uptake ◽  
Adenosine A2a Receptors ◽  
A2a Receptors ◽  
Cultured Astrocytes ◽  
Adenosine A2a

Late onset and increasing expression of the gap junction protein connexin30 in adult murine brain and long-term cultured astrocytes

Glia ◽  
1999 ◽  
Vol 25 (2) ◽  
pp. 111-119 ◽  
Author(s):  
P. Kunzelmann ◽  
W. Schr�der ◽  
O. Traub ◽  
C. Steinh�user ◽  
R. Dermietzel ◽  
...  
Keyword(s):  
Gap Junction ◽  
Late Onset ◽  
Cultured Astrocytes ◽  
Junction Protein ◽  
Gap Junction Protein ◽  
Murine Brain

Effects of SSRI on L-glutamate uptake activity of cultured astrocytes

2009 ◽  
Vol 65 ◽  
pp. S87
Author(s):  
Junpei Takaki ◽  
Jun-Ichi Kuriwaki ◽  
Kaoru Sato ◽  
Takeshi Suzuki
Keyword(s):  
Glutamate Uptake ◽  
Cultured Astrocytes ◽  
Uptake Activity

scholarly journals 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Decreases Glutamate Uptake in Cultured Astrocytes

2002 ◽  
Vol 68 (5) ◽  
pp. 2216-2219 ◽  
Author(s):  
Alan S. Hazell ◽  
Yossef Itzhak ◽  
Huaping Liu ◽  
Michael D. Norenberg
Keyword(s):  
Glutamate Uptake ◽  
Cultured Astrocytes

Deep Hypothermia and Rewarming Alters Glutamate Levels and Glycogen Content in Cultured Astrocytes 

1999 ◽  
Vol 91 (6) ◽  
pp. 1763-1763 ◽  
Author(s):  
Bruno Bissonnette ◽  
Luc Pellerin ◽  
Patrick Ravussin ◽  
Véronique B. Daven ◽  
Pierre J. Magistretti
Keyword(s):  
Glycogen Content ◽  
Glutamate Uptake ◽  
Primary Cultures ◽  
Deep Hypothermia ◽  
Extracellular Glutamate ◽  
Mild Hyperthermia ◽  
Extracellular Concentration ◽  
Sequence Of Events ◽  
Cultured Astrocytes

Background Deep hypothermia has been associated with an increased incidence of postoperative neurologic dysfunction after cardiac surgery in children. Recent studies suggest an excitotoxic mechanism involving overstimulation of glutamate receptors. Extracellular glutamate uptake occurs primarily by astrocytes. Astrocytes also store glycogen, which may be used to sustain the energy-consuming glutamate uptake. Extracellular glutamate and glycogen content were studied during temperature changes mimicking cardiopulmonary bypass in vivo. Methods Primary cultures of cerebral cortical astrocytes were used in a specially designed incubator allowing continuous changes of temperature and ambient gas concentrations. The sequence of events was as follows: normothermia, rapid cooling (2.8 degrees C/min) followed by 60 min of deep hypothermia (15 degrees C), followed by rewarming (3.0 degrees C/min) and subsequent 5 h of mild hyperthermia (38.5 degrees C). Two different conditions of oxygenation were studied: (1) normoxia (25% O2, 70% N2, 5% CO2); or (2) hyperoxia (95% O2, 5% CO2). The extracellular glutamate concentrations and intracellular glycogen levels were measured at nine time points. Results One hundred sixty-two cultures were studied in four independent experiments. The extracellular concentration of glutamate in the normoxic group increased significantly from 35+/-10 nM/mg protein at baseline up to 100+/-15 nM/mg protein at the end of 5 h of mild hyperthermia (P < 0.05). In contrast, extracellular glutamate levels did not vary from control in the hyperoxic group. Glycogen levels decreased significantly from 260+/-85 nM/mg protein at baseline to < 25+/-5 nM/mg protein at the end of 5 h in the normoxic group (P < 0.05) but returned to control levels after rewarming in the hyperoxic group. No morphologic changes were observed in either group. Conclusion The extracellular concentration of glutamate increases, whereas the intracellular glycogen content decreases when astrocytes are exposed to a sequence of deep hypothermia and rewarming. This effect of hypothermia is prevented when astrocytes are exposed to hyperoxic conditions.

scholarly journals Array analysis of gene expression in connexin-43 null astrocytes

2003 ◽  
Vol 15 (3) ◽  
pp. 177-190 ◽  
Author(s):  
Dumitru A. Iacobas ◽  
Marcia Urban-Maldonado ◽  
Sanda Iacobas ◽  
Eliana Scemes ◽  
David C. Spray
Keyword(s):  
Gene Expression ◽  
Gap Junction ◽  
Dna Sequences ◽  
Connexin 43 ◽  
Expression Patterns ◽  
Dna Arrays ◽  
Cultured Astrocytes ◽  
Junction Protein ◽  
High Degree ◽  
The Impact

Connexin-43 (Cx43) is the most abundant gap junction protein in brain, where it is found primarily between astrocytes. Although the morphology of astrocytes from Cx43-null (knockout, KO) mice is similar to that of wild-type (WT) astrocytes, KO astrocytes exhibit reduced growth rate in culture. To evaluate the impact of deletion of Cx43 on other genes, including those encoding cell cycle proteins, we used DNA arrays to determine expression patterns in cultured astrocytes from sibling Cx43-null and WT mice. RNA samples extracted from astrocytes cultured from WT and Cx43-null neonatal mice were dye labeled and individually cohybridized with a reference of labeled cDNAs pooled from a variety of tissues on 8 gene arrays containing 8,975 mouse DNA sequences. Normal variability in expression of each gene was evaluated and incorporated into “expression scores” to statistically compare expression levels between WT and KO samples. In Cx43-null astrocytes, 4.1% of the 4,998 adequately quantifiable spots were found to have significantly ( P < 0.05) decreased hybridization compared with controls, and 9.4% of the spots showed significantly higher hybridization. The significantly different spots corresponded to RNAs encoding 252 known proteins, many not previously linked to gap junctions, including transcription factors, channels and transporters, cell growth and death signals, enzymes and cell adhesion molecules. These data indicate a surprisingly high degree of impact of deletion of Cx43 on other astrocyte genes, implying that gap junction gene expression alters numerous processes in addition to intercellular communication.

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