Fig. 3.
Dexmedetomidine acts through phosphorylated extracellular signal–regulated kinase– and brain-derived neurotrophic factor (BDNF)–dependent pathways. (A, B) Representative Western blots and summarized data of the phosphorylated extracellular signal–regulated kinase (A) and the total extracellular signal–regulated kinase (B). β-Actin was used as a loading control. (A) n = 6; P = 0.002; nonparametric Mann–Whitney U test. (B) n = 4; unpaired Student’s t test. The molecular weight (MW) is shown as kDa. (C) Extracellular signal–regulated kinase inhibitor PD98059 (PD, 50 µM) blocked dexmedetomidine attenuation of etomidate-induced increase in tonic current. Treating astrocytes with PD98059 alone had no effect on the tonic current. (Left) n = 5, 6, 6, 7 (left to right); one-way ANOVA, F(3,20) = 12.6, P < 0.0001; Tukey’s multiple comparisons test. (Right) n = 5, 6 (left to right); unpaired Student’s t test, P = 0.29. (D) Conditioned medium from astrocytes treated with dexmedetomidine (0.1 µM) could prevent the etomidate-induced increase in tonic current in neurons. Heating the conditioned medium abolished this effect. n = 8, 11, 12 (left to right); one-way ANOVA, F(2,28) = 5.6, P = 0.009; Tukey’s multiple comparisons test. (E) Representative curves and summarized data show that the level of brain-derived neurotrophic factor messenger RNA was increased in the conditioned medium from astrocytes treated with dexmedetomidine (0.1 µM). n = 8, *P = 0.042, unpaired Student’s t test. (F) brain-derived neurotrophic factor in medium from astrocytes treated with dexmedetomidine (0.1 to 10 µM) was measured with enzyme-linked immunosorbent assay. Levels were detected only when astrocytes were treated with dexmedetomidine at concentrations greater than 0.01 µM. n = 5. (G) Brain-derived neurotrophic factor mimicked dexmedetomidine and prevented etomidate-induced increase in tonic current. n = 8, 7, 8, 6 (left to right); one-way ANOVA, F(3,25) = 16.6, P < 0.0001; Tukey’s multiple comparisons test. (H) Brain-derived neurotrophic factor receptor (tropomyosin receptor kinase B [TrkB]) antagonist ANA 12 blocked the effects of dexmedetomidine. n = 8, 11, 12, 9, 7 (left to right); one-way ANOVA, F(4,42) = 7.7, P < 0.0001; Tukey’s multiple comparisons test. The data are means ± SD. * = P < 0.05; ** = P < 0.01; *** = P < 0.001. Ctrl = control; Dex = dexmedetomidine; Etom = etomidate; N.S. = not significant.

Dexmedetomidine acts through phosphorylated extracellular signal–regulated kinase– and brain-derived neurotrophic factor (BDNF)–dependent pathways. (A, B) Representative Western blots and summarized data of the phosphorylated extracellular signal–regulated kinase (A) and the total extracellular signal–regulated kinase (B). β-Actin was used as a loading control. (A) n = 6; P = 0.002; nonparametric Mann–Whitney U test. (B) n = 4; unpaired Student’s t test. The molecular weight (MW) is shown as kDa. (C) Extracellular signal–regulated kinase inhibitor PD98059 (PD, 50 µM) blocked dexmedetomidine attenuation of etomidate-induced increase in tonic current. Treating astrocytes with PD98059 alone had no effect on the tonic current. (Left) n = 5, 6, 6, 7 (left to right); one-way ANOVA, F(3,20) = 12.6, P < 0.0001; Tukey’s multiple comparisons test. (Right) n = 5, 6 (left to right); unpaired Student’s t test, P = 0.29. (D) Conditioned medium from astrocytes treated with dexmedetomidine (0.1 µM) could prevent the etomidate-induced increase in tonic current in neurons. Heating the conditioned medium abolished this effect. n = 8, 11, 12 (left to right); one-way ANOVA, F(2,28) = 5.6, P = 0.009; Tukey’s multiple comparisons test. (E) Representative curves and summarized data show that the level of brain-derived neurotrophic factor messenger RNA was increased in the conditioned medium from astrocytes treated with dexmedetomidine (0.1 µM). n = 8, *P = 0.042, unpaired Student’s t test. (F) brain-derived neurotrophic factor in medium from astrocytes treated with dexmedetomidine (0.1 to 10 µM) was measured with enzyme-linked immunosorbent assay. Levels were detected only when astrocytes were treated with dexmedetomidine at concentrations greater than 0.01 µM. n = 5. (G) Brain-derived neurotrophic factor mimicked dexmedetomidine and prevented etomidate-induced increase in tonic current. n = 8, 7, 8, 6 (left to right); one-way ANOVA, F(3,25) = 16.6, P < 0.0001; Tukey’s multiple comparisons test. (H) Brain-derived neurotrophic factor receptor (tropomyosin receptor kinase B [TrkB]) antagonist ANA 12 blocked the effects of dexmedetomidine. n = 8, 11, 12, 9, 7 (left to right); one-way ANOVA, F(4,42) = 7.7, P < 0.0001; Tukey’s multiple comparisons test. The data are means ± SD. * = P < 0.05; ** = P < 0.01; *** = P < 0.001. Ctrl = control; Dex = dexmedetomidine; Etom = etomidate; N.S. = not significant.

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