RESUMO
BACE1 is an indispensable enzyme for generating ß-amyloid peptides, which are excessively accumulated in brains of Alzheimer's patients. However, BACE1 is also required for proper myelination of peripheral nerves, as BACE1-null mice display hypomyelination. To determine the precise effects of BACE1 on myelination, here we have uncovered a role of BACE1 in the control of Schwann cell proliferation during development. We demonstrate that BACE1 regulates the cleavage of Jagged-1 and Delta-1, two membrane-bound ligands of Notch. BACE1 deficiency induces elevated Jag-Notch signaling activity, which in turn facilitates proliferation of Schwann cells. This increase in proliferation leads to shortened internodes and decreased Schmidt-Lanterman incisures. Functionally, evoked compound action potentials in BACE1-null nerves were significantly smaller and slower, with a clear decrease in excitability. BACE1-null nerves failed to effectively use lactate as an alternative energy source under conditions of increased physiological activity. Correlatively, BACE1-null mice showed reduced performance on rotarod tests. Collectively, our data suggest that BACE1 deficiency enhances proliferation of Schwann cell due to the elevated Jag1/Delta1-Notch signaling, but fails to myelinate axons efficiently due to impaired the neuregulin1-ErbB signaling, which has been documented.
Assuntos
Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Proliferação de Células/fisiologia , Células de Schwann/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Animais , Ácido Aspártico Endopeptidases/genética , Axônios/metabolismo , Proliferação de Células/genética , Camundongos Knockout , Bainha de Mielina/metabolismo , Neurogênese/genética , Neurogênese/fisiologia , Células de Schwann/citologia , Nervo Isquiático/metabolismo , Transdução de Sinais/fisiologiaRESUMO
We report aluminum based structures for manipulation of surface plasmon polariton (SPP) propagation at short wavelength range. Our simulation shows that aluminum is a good metal to excite and propagate SPPs with blue light and that the SPP wavelength can be reduced from about 465 nm to about 265 nm by monitoring the thickness of a coated Si(3)N(4) layer above the aluminum film. It is also shown that the damping becomes more significant with the increase of the thickness of the Si(3)N(4) layer. We also experimentally demonstrated the SPP wavelength tuning effect for 20nm Si(3)N(4) layer covered Al, which can be explained by the variation of effective permittivity. The proposed Metal-Insulator-Air (MIA) structures with SPP wavelength tuning ability have potential applications in 2D optics.