Intraepidermal nerve fiber density (IENFD) normative values for clinical use.

<p>Intraepidermal nerve fiber density (IENFD) normative values for clinical use.</p

PGP 9.5-immunolabeled intraepidermal nerve fibers (IENFs).

<p>A: IENFs regularly distributed in the epidermis in a young man; B: Long horizontal branchings of IENFs in the upper epidermis; C: Small swellings (arrows) and one large swelling (arrow head) on an IENF; D: Isolated large swelling along an IENF.</p

Demographic and biological data of the healthy subjects (n = 300) included in the study.

<p>Demographic and biological data of the healthy subjects (n = 300) included in the study.</p

Flow chart indicating the number of healthy subjects and biopsies analyzed in the study.

<p>Twenty-seven volunteers failed screening for inclusion in the study. Among them, 23 subjects were at risk of neuropathy for reasons that included diabetes, renal insufficiency, positive serology for HCV or HBV, and absence of deep tendon reflex. Four subjects had a contraindication to skin biopsy (HTA [xylocaine injection], limb surgery, pregnancy, or prohibited therapy).</p

Intraepidermal nerve fiber density.

<p>Scatterplot showing intraepidermal nerve fiber density (IENFD) values in the distal leg in healthy subjects according to gender and age (A: women, B: men). Line depicts 5th percentile.</p

Merkel cells following PGP 9.5 immunolabeling.

<p>A-B: Isolated Merkel cells or touch dome in the basal epidermal layer; C-D: Epidermal cluster of Merkel cells; B and D show that only nerve terminals filled with mitochondria are immunolabeled.</p

Neurogenesis in the vomeronasal epithelium.

<p>Localisation and mean density of BrdU (A–C), Ki67 (D–F), cleaved caspase 3 (G–I), GAP 43 (J–L), doublecortin (M–O) and OMP (P–R) labelled cells in the vomeronasal epithelium of WT and STOP null mice. The x-axis refers to the three levels studied, from rostral (level 1) to caudal (level 3), where the vomeronasal organ was present. A statistically significant increase in proliferating (BrdU and Ki67 positive cells), apoptotic (caspase 3 positive cells) and immature neurons (GAP 43 and doublecortin positive cells), but not mature OMP positive neurons was observed in STOP null mice as compared to WT mice. All values are represented as mean +/− SEM, *p<0.05, **p<0.01. Scale bar: 100 µm.</p

Ultrastructure of olfactory bulb glomeruli.

<p>Electron microscopy micrographs of olfactory bulb glomeruli in WT (A) and STOP null (B–F) mice at 3 to 6 months of age. In STOP null mice, olfactory axon endings are filled with autophagic-like structures (B, arrow), tubulovesicular profiles (C, arrowhead), or both (D). When few autophagic structures were present (arrows) (E, F), olfactory axons endings could be identified by the presence of synaptic vesicles and postsynaptic densities (arrowheads) (E, F). De: dentrite; OA: olfactory axon. Scale bar: 0,5 µm (A, C, E, F); 1 µm (B, D).</p

Regeneration of the olfactory epithelium.

<p>Mean epithelial OMP positive area before and after regeneration at the three levels 4, 5, 6 in WT and STOP null mice at two different ages. The x-axis refers to the three levels studied, from rostral (level 4) to caudal (level 6), where turbinates are most developed and olfactory epithelium most abundant. There is no difference in the ability of olfactory epithelium to regenerate at the three levels studied between WT and STOP null mice in 3 month-old (A) and 10 month-old (B) animals. All values are represented as mean +/− SEM, *p<0.05. The photomicrographs in A and B illustrate OMP immunostaining in the olfactory epithelium of animals after regeneration. Scale bar: 500 µm.</p

Glomerular structure after regeneration in 10-month-old mice.

<p>Localisation of Vglut2 (A–D) and OMP (E–H) immunolabelling in olfactory bulb glomeruli of WT (A, C, E, G) and STOP null (B, D, F H) mice in controls (A, B, E, F) and after regeneration (C, D, G, H). Note the characteristic feature of a mosaicism between Vglut2 or OMP positive fibers and Vglut2 or OMP negative dentrites in WT mice either in controls or after regeneration (A, E and C, G respectively). In STOP null mice, a clumped aspect of either Vglut2 (D) or OMP (H) positive fibers was observed. Scale bar: 20 µm.</p