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. 2019 Oct 30;39(44):8816–8825. doi: 10.1523/JNEUROSCI.0617-19.2019

Figure 6.

Figure 6.

Nimodipine can restore the neurophysiological responses to ghrelin in arcuate NPY neurons treated with oligomeric Aβ1–42. A, B, Brain slices containing hypothalamic arcuate nucleus from young (3- to 4-month-old) NPY-GFP mice were used for whole-cell patch-clamp recordings. Application of ghrelin (100 nm) depolarized the membrane potential and increased spike frequency of arcuate NPY neurons. Exogenous oliogmeric Aβ1–42 (100 nm) depolarized the membrane potential of arcuate NPY neurons and inhibited its response to ghrelin (100 nm). Nimodipine (NMD, 2 μm) restored the ghrelin-mediated depolarization of arcuate NPY neurons treated with exogenous oligomeric Aβ1–42. Statistical analysis: two-tailed paired Student test for comparison of vehicle to ghrelin-treated arcuate NPY neurons (membrane potential: t = 6.444, df = 15, p < 0.001, n = 16 cells from 13 mice per group; spike frequency: t = 3.742, df = 13, p = 0.0025, n = 14 cells from 12 mice per group). Repeated-measures one-way ANOVA comparing vehicle, Aβ1–42, and ghrelin treatments (membrane potential: F(1.579, 12.63) = 7.577, p = 0.0096, n = 9 cells from 5 mice per group; spike frequency: F(1.365, 9.557) = 3.941, p = 0.0679, n = 8 cells from 5 mice per group), followed by post hoc Tukey's multiple comparisons. Repeated-measures one-way ANOVA comparing vehicle, Aβ1–42, nimodipine, and ghrelin treatments (membrane potential: F(1.883, 11.30) = 8.785, p = 0.0014, n = 7 cells from 4 mice per group; spike frequency: F(2.125, 12.75) = 3.220, p = 0.0716, n = 7 cells from 4 mice per group) followed by post hoc Tukey's multiple comparisons. *p < 0.05. **p < 0.01. ***p < 0.001. Data are mean ± SEM. C, Nimodipine restored the ghrelin-mediated increase in cytoplasmic-free Ca2+ levels in arcuate NPY neurons treated with exogenous oligomeric Aβ1–42. Cytoplasmic-free Ca2+ was measured using fura-2 AM in arcuate NPY neurons isolated by enzymatic digestion from young (3- to 4-month-old) WT NPY-GFP mice. After obtaining baseline levels, cells were perfused sequentially with oligomeric Aβ1–42 (100 nm), nimodipine (2 μm), and then ghrelin (100 nm). Statistical analysis: repeated-measures one-way ANOVA comparing vehicle, Aβ1–42, nimodipine, and ghrelin treatments (F(2.128, 44.69) = 13.90, p < 0.0001, n = 22 cells from 4 mice) followed by post hoc Tukey's multiple comparisons. *p < 0.05. **p < 0.01. ***p < 0.001. Data are mean ± SEM.