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. 2022 May 19;13:2785. doi: 10.1038/s41467-022-30466-6

Fig. 7. Col1a2 secretion is regulated by HCN channel-regulated sensory neuron activity.

Fig. 7

A, B TTX (1 µM; A; vehicle n = 6, TTX n = 6; P < 0.0001) and lamotrigine (LTR; 200 µM; B; vehicle n = 9, LTR n = 9; P = 0.0001) reduce Nf1+/neo DRG neuron Col1a2 secretion by 73 and 47% relative to vehicle-treated controls. C ZD7288 (ZD; 30 µM) increases Col1a2 secretion in WT (n = 10 in both groups; P < 0.0001) and Nf1+/1809 (n = 4 in both groups; P = 0.0103) DRG neurons. D RAS activity is increased in both Nf1+/neo and Nf1+/1809 DRG neurons relative to controls (n = 5 in all groups; P < 0.0001), (E) and is inhibited following TTX and LTR treatment (n = 6 in all groups; P < 0.0001). F, G IN-1 has no effect on DRG neuronal activity, as measured by (F) multi-electrode array (vehicle n = 6, IN-1 n = 3, ns not significant), or (G) calcium-imaging recordings (vehicle n = 18, IN-1 n = 18; ns, not significant). Right: representative (F) spike plots of entire multi-electrode array well recordings over 30 s, and (G) traces of neuronal activity over 3 min. H IN-1 reduces Col1a2 secretion by 77.9% in Nf1+/neo DRG neurons. n = 6 for both groups, P = 0.0001. I IN-1 reduces proliferation by 50% in Nf1−/− DRG–NSCs. n = 6 for both groups, P < 0.0001. J Lamotrigine treatment decreases pNF progression in vivo. Gross images and representative immunostaining of mouse pNFs demonstrate that LTR treatment reduces pNF size, partly restores neuronal histology (H&E), reduces proliferation (Ki67+ cells) and decreases Col1a2 production. Scale bars: gross anatomy images, 1 mm; sections, 100 µm. n = 5 for both groups. Data are represented as means ± SEM (A–C, H, I) using two-tailed paired Student’s t tests, (F, G) two-tailed unpaired t tests, or (D, E) one-way ANOVA with Dunnett’s post-test correction. P values are indicated within each panel. ns, not significant. Source data are provided as a Source Data file.