Loss of STOP Protein Impairs Peripheral Olfactory Neurogenesis

International audienceIn conclusion, STOP protein seems to be involved in the establishment of synapses in the olfactory glomerulus. Our results indicate that the olfactory system of STOP null mice is a well-suited experimental model (1) for the study of the mechanism of action of STOP protein in synaptic function/plasticity and (2) for pathophysiological studies of the mechanisms of altered neuronal connections in schizophrenia

p70S6 kinase regulates oligodendrocyte differentiation and is active in remyelinating lesions

International audienceThe p70 ribosomal S6 kinases (p70 ribosomal S6 kinase 1 and p70 ribosomal S6 kinase 2) are downstream targets of the mechanistic target of rapamycin signalling pathway. p70 ribosomal S6 kinase 1 specifically has demonstrated functions in regulating cell size in Drosophila and in insulin-sensitive cell populations in mammals. Prior studies demonstrated that the mechanistic target of the rapamycin pathway promotes oligodendrocyte differentiation and developmental myelination; however, how the immediate downstream targets of mechanistic target of rapamycin regulate these processes has not been elucidated. Here, we tested the hypothesis that p70 ribosomal S6 kinase 1 regulates oligodendrocyte differentiation during developmental myelination and remyelination processes in the CNS. We demonstrate that p70 ribosomal S6 kinase activity peaks in oligodendrocyte lineage cells at the time when they transition to myelinating oligodendrocytes during developmental myelination in the mouse spinal cord. We further show p70 ribosomal S6 kinase activity in differentiating oligodendrocytes in acute demyelinating lesions induced by lysophosphatidylcholine injection or by experimental autoimmune encephalomyelitis in mice. In demyelinated lesions, the expression of the p70 ribosomal S6 kinase target, phosphorylated S6 ribosomal protein, was transient and highest in maturing oligodendrocytes. Interestingly, we also identified p70 ribosomal S6 kinase activity in oligodendrocyte lineage cells in active multiple sclerosis lesions. Consistent with its predicted function in promoting oligodendrocyte differentiation, we demonstrate that specifically inhibiting p70 ribosomal S6 kinase 1 in cultured oligodendrocyte precursor cells significantly impairs cell lineage progression and expression of myelin basic protein. Finally, we used zebrafish to show in vivo that inhibiting p70 ribosomal S6 kinase 1 function in oligodendroglial cells reduces their differentiation and the number of myelin internodes produced. These data reveal an essential function of p70 ribosomal S6 kinase 1 in promoting oligodendrocyte differentiation during development and remyelination across multiple species

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

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

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

L'Avenir de Luchon : journal scientifique, littéraire, annonces et réclames : guide général des baigneurs et des touristes aux eaux thermales, bains de mer de la France et de l'étranger

30 avril 19221922/04/30 (N91)-1922/04/30.Appartient à l’ensemble documentaire : MidiPyren

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

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

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