RESUMO
The conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of ß-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Doenças Neurodegenerativas/metabolismo , Sono/fisiologia , Antagonistas Adrenérgicos/administração & dosagem , Animais , Encéfalo/fisiologia , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiologia , Líquido Cefalorraquidiano/metabolismo , Difusão , Eletroencefalografia , Espaço Extracelular , Espaço Intracelular , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Compostos de Amônio Quaternário/química , Receptores Adrenérgicos/metabolismo , Vigília/fisiologiaRESUMO
The processes by which blood flow is regulated at the capillary network level in the brain has been a source of continual debate. It is generally accepted that cerebral blood flow regulation occurs primarily at the arteriolar level. It has been recently suggested, however, that the capillary network is likewise under dynamic regulation. The exact mechanisms of capillary regulation remain unknown. Previously, the limiting factor in determining how the cerebrovascular network is regulated has been the speed at which multiphoton images of large (~200µm2) capillary and arteriole systems can be acquired. Conventional laser scanning microscopy systems are temporally limited in two dimensions. We have developed a Random Access Multiphoton (RAMP) microscope, which operates on the principles of Acousto-optic beam scanning and therefore has no moving parts, specifically for the purpose of imaging blood flow virtually simultaneously throughout the capillary network. We demonstrate the ability to survey blood flow simultaneously in 100 capillaries.
RESUMO
In vivo imaging of cells gives a glimpse into the world of biology in a natural setting unparalleled by any other venue. Two-photon imaging of fluorescently labeled cells has become the standard to obtain high-resolution, dynamic images of living specimens with great specificity. This review focuses on providing the reader with a short history of, and impetus behind, two-photon imaging, its working mechanics, and emerging technologies related to biological multiphoton imaging.