Astrocyte-Conditioned Medium Protects Prefrontal Cortical Neurons from Glutamate-Induced Cell Death by Inhibiting TNF-α Expression

Cai Song, Yih Shyuan Wu, Zhi You Yang, Allan V. Kalueff, Yin Yin Tsao, Yilong Dong, Kuan Pin Su

Результат исследований: Научные публикации в периодических изданияхстатья

Выдержка

Objective: Both excitotoxicity and neurotrophin deficiency may contribute to the etiology of depression and neurodegeneration. Astrocytes not only regulate glutamate metabolism and clearance, they also produce neurotrophins in the brain. However, the direct interaction between neurons and astrocytes remains unknown. Methods: This study evaluated the cellular mechanisms by which astrocyte-conditioned medium (ACM) protects prefrontal cortical neurons from glutamate-induced death by measuring cell viability and morphology as well as mRNA and protein expression of brain-derived neurotrophic factor (BDNF), BDNF receptors, glial cell line-derived neurotrophic factor (GDNF), and the proinflammatory cytokine, tumor necrosis factor (TNF)-α. Neurons and astrocytes were purified from the brains of neonatal 1-day-old Sprague-Dawley rats. ACM was harvested after exposing astrocytes to culture medium containing 100 μM glutamate for 48 h. Results: Glutamate insult (100 μM for 6 h) significantly reduced neuronal cell viability and increased the mRNA expression of BDNF. Glutamate (24 h) decreased neuronal viability and the expression of BDNF, but increased mRNA expression of GFAP, p75 neurotrophin receptor (p75NTR), and TNF-α. ACM pretreatment (2 h) reversed glutamate-decreased cell viability and increased BDNF, but reduced the expression of GDNF, P75NTR, and TNF-α at the mRNA level. Western blotting generally confirmed the mRNA expression following 24 glutamate insults. Furthermore, the glutamate-induced decrease in the protein expression of BDNF and full-length TrkB receptor and increase in pro-BDNF, truncated TrkB isoform 1 receptor, p75NTR, GDNF, and TNF-α were significantly attenuated by ACM pretreatment. Conclusions: The study demonstrates that ACM exerts neuroprotective effects on cell viability, and this effect is most likely mediated through the modulation of neurotrophin and TNF-α expression.

Язык оригиналаанглийский
Страницы (с-по)33-42
ЖурналNeuroImmunoModulation
Том26
Номер выпуска1
DOI
СостояниеОпубликовано - 2019

Отпечаток

Conditioned Culture Medium
Astrocytes
Glutamic Acid
Cell Death
Tumor Necrosis Factor-alpha
Brain-Derived Neurotrophic Factor
Neurons
Glial Cell Line-Derived Neurotrophic Factor
Cell Survival
Nerve Growth Factors
Messenger RNA
trkB Receptor
Nerve Growth Factor Receptor
Brain
Neuroprotective Agents
Sprague Dawley Rats
Culture Media
Protein Isoforms
Proteins
Western Blotting

Предметные области Scopus

  • Эндокринные и аутоиммунные системы
  • Неврология
  • Эндокринология
  • Иммунология

Цитировать

Song, Cai ; Wu, Yih Shyuan ; Yang, Zhi You ; Kalueff, Allan V. ; Tsao, Yin Yin ; Dong, Yilong ; Su, Kuan Pin. / Astrocyte-Conditioned Medium Protects Prefrontal Cortical Neurons from Glutamate-Induced Cell Death by Inhibiting TNF-α Expression. В: NeuroImmunoModulation. 2019 ; Том 26, № 1. стр. 33-42.
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title = "Astrocyte-Conditioned Medium Protects Prefrontal Cortical Neurons from Glutamate-Induced Cell Death by Inhibiting TNF-α Expression",
abstract = "Objective: Both excitotoxicity and neurotrophin deficiency may contribute to the etiology of depression and neurodegeneration. Astrocytes not only regulate glutamate metabolism and clearance, they also produce neurotrophins in the brain. However, the direct interaction between neurons and astrocytes remains unknown. Methods: This study evaluated the cellular mechanisms by which astrocyte-conditioned medium (ACM) protects prefrontal cortical neurons from glutamate-induced death by measuring cell viability and morphology as well as mRNA and protein expression of brain-derived neurotrophic factor (BDNF), BDNF receptors, glial cell line-derived neurotrophic factor (GDNF), and the proinflammatory cytokine, tumor necrosis factor (TNF)-α. Neurons and astrocytes were purified from the brains of neonatal 1-day-old Sprague-Dawley rats. ACM was harvested after exposing astrocytes to culture medium containing 100 μM glutamate for 48 h. Results: Glutamate insult (100 μM for 6 h) significantly reduced neuronal cell viability and increased the mRNA expression of BDNF. Glutamate (24 h) decreased neuronal viability and the expression of BDNF, but increased mRNA expression of GFAP, p75 neurotrophin receptor (p75NTR), and TNF-α. ACM pretreatment (2 h) reversed glutamate-decreased cell viability and increased BDNF, but reduced the expression of GDNF, P75NTR, and TNF-α at the mRNA level. Western blotting generally confirmed the mRNA expression following 24 glutamate insults. Furthermore, the glutamate-induced decrease in the protein expression of BDNF and full-length TrkB receptor and increase in pro-BDNF, truncated TrkB isoform 1 receptor, p75NTR, GDNF, and TNF-α were significantly attenuated by ACM pretreatment. Conclusions: The study demonstrates that ACM exerts neuroprotective effects on cell viability, and this effect is most likely mediated through the modulation of neurotrophin and TNF-α expression.",
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author = "Cai Song and Wu, {Yih Shyuan} and Yang, {Zhi You} and Kalueff, {Allan V.} and Tsao, {Yin Yin} and Yilong Dong and Su, {Kuan Pin}",
year = "2019",
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Astrocyte-Conditioned Medium Protects Prefrontal Cortical Neurons from Glutamate-Induced Cell Death by Inhibiting TNF-α Expression. / Song, Cai; Wu, Yih Shyuan; Yang, Zhi You; Kalueff, Allan V.; Tsao, Yin Yin; Dong, Yilong; Su, Kuan Pin.

В: NeuroImmunoModulation, Том 26, № 1, 2019, стр. 33-42.

Результат исследований: Научные публикации в периодических изданияхстатья

TY - JOUR

T1 - Astrocyte-Conditioned Medium Protects Prefrontal Cortical Neurons from Glutamate-Induced Cell Death by Inhibiting TNF-α Expression

AU - Song, Cai

AU - Wu, Yih Shyuan

AU - Yang, Zhi You

AU - Kalueff, Allan V.

AU - Tsao, Yin Yin

AU - Dong, Yilong

AU - Su, Kuan Pin

PY - 2019

Y1 - 2019

N2 - Objective: Both excitotoxicity and neurotrophin deficiency may contribute to the etiology of depression and neurodegeneration. Astrocytes not only regulate glutamate metabolism and clearance, they also produce neurotrophins in the brain. However, the direct interaction between neurons and astrocytes remains unknown. Methods: This study evaluated the cellular mechanisms by which astrocyte-conditioned medium (ACM) protects prefrontal cortical neurons from glutamate-induced death by measuring cell viability and morphology as well as mRNA and protein expression of brain-derived neurotrophic factor (BDNF), BDNF receptors, glial cell line-derived neurotrophic factor (GDNF), and the proinflammatory cytokine, tumor necrosis factor (TNF)-α. Neurons and astrocytes were purified from the brains of neonatal 1-day-old Sprague-Dawley rats. ACM was harvested after exposing astrocytes to culture medium containing 100 μM glutamate for 48 h. Results: Glutamate insult (100 μM for 6 h) significantly reduced neuronal cell viability and increased the mRNA expression of BDNF. Glutamate (24 h) decreased neuronal viability and the expression of BDNF, but increased mRNA expression of GFAP, p75 neurotrophin receptor (p75NTR), and TNF-α. ACM pretreatment (2 h) reversed glutamate-decreased cell viability and increased BDNF, but reduced the expression of GDNF, P75NTR, and TNF-α at the mRNA level. Western blotting generally confirmed the mRNA expression following 24 glutamate insults. Furthermore, the glutamate-induced decrease in the protein expression of BDNF and full-length TrkB receptor and increase in pro-BDNF, truncated TrkB isoform 1 receptor, p75NTR, GDNF, and TNF-α were significantly attenuated by ACM pretreatment. Conclusions: The study demonstrates that ACM exerts neuroprotective effects on cell viability, and this effect is most likely mediated through the modulation of neurotrophin and TNF-α expression.

AB - Objective: Both excitotoxicity and neurotrophin deficiency may contribute to the etiology of depression and neurodegeneration. Astrocytes not only regulate glutamate metabolism and clearance, they also produce neurotrophins in the brain. However, the direct interaction between neurons and astrocytes remains unknown. Methods: This study evaluated the cellular mechanisms by which astrocyte-conditioned medium (ACM) protects prefrontal cortical neurons from glutamate-induced death by measuring cell viability and morphology as well as mRNA and protein expression of brain-derived neurotrophic factor (BDNF), BDNF receptors, glial cell line-derived neurotrophic factor (GDNF), and the proinflammatory cytokine, tumor necrosis factor (TNF)-α. Neurons and astrocytes were purified from the brains of neonatal 1-day-old Sprague-Dawley rats. ACM was harvested after exposing astrocytes to culture medium containing 100 μM glutamate for 48 h. Results: Glutamate insult (100 μM for 6 h) significantly reduced neuronal cell viability and increased the mRNA expression of BDNF. Glutamate (24 h) decreased neuronal viability and the expression of BDNF, but increased mRNA expression of GFAP, p75 neurotrophin receptor (p75NTR), and TNF-α. ACM pretreatment (2 h) reversed glutamate-decreased cell viability and increased BDNF, but reduced the expression of GDNF, P75NTR, and TNF-α at the mRNA level. Western blotting generally confirmed the mRNA expression following 24 glutamate insults. Furthermore, the glutamate-induced decrease in the protein expression of BDNF and full-length TrkB receptor and increase in pro-BDNF, truncated TrkB isoform 1 receptor, p75NTR, GDNF, and TNF-α were significantly attenuated by ACM pretreatment. Conclusions: The study demonstrates that ACM exerts neuroprotective effects on cell viability, and this effect is most likely mediated through the modulation of neurotrophin and TNF-α expression.

KW - Astrocytes

KW - Cell viability

KW - Glutamate

KW - Neurotrophic factors

KW - Tumor necrosis factor-α

KW - SYSTEM

KW - DEPRESSION

KW - NEUROTROPHIC FACTOR

KW - HIPPOCAMPAL

KW - SIZE

KW - DENSITY

KW - Tumor necrosis factor-alpha

KW - GDNF

KW - CORTEX

KW - SECRETION

KW - RECEPTORS

UR - http://www.scopus.com/inward/record.url?scp=85060999086&partnerID=8YFLogxK

U2 - 10.1159/000495211

DO - 10.1159/000495211

M3 - Article

AN - SCOPUS:85060999086

VL - 26

SP - 33

EP - 42

JO - NeuroImmunoModulation

JF - NeuroImmunoModulation

SN - 1021-7401

IS - 1

ER -