In vivo NADH fluorescence imaging indicates effect of aquaporin-4 deletion on oxygen microdistribution in cortical spreading depression

1] Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York, USA [2] Centre for Molecular Biology and Neuroscience, Letten Centre, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway [3] Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism (Impact Factor: 5.41). 04/2013; 33(7). DOI: 10.1038/jcbfm.2013.63
Source: PubMed

ABSTRACT Using in vivo two-photon imaging, we show that mice deficient in aquaporin-4 (AQP4) display increased fluorescence of nicotinamide adenine dinucleotide (NADH) when subjected to cortical spreading depression. The increased NADH signal, a proxy of tissue hypoxia, was restricted to microwatershed areas remote from the vasculature. Aqp4 deletion had no effects on the hyperemia response, but slowed [K(+)]o recovery. These observations suggest that K(+) uptake is suppressed in Aqp4(-/-) mice as a consequence of decreased oxygen delivery to tissue located furthest away from the vascular source of oxygen, although increased oxygen consumption may also contribute to our observations.Journal of Cerebral Blood Flow & Metabolism advance online publication, 24 April 2013; doi:10.1038/jcbfm.2013.63.

39 Reads
  • Source
    • "It is now understood that polarity of astrocytes and neurons is critical to their normal function and that loss of polarity plays a role in a number of diseases. Pioneering research on astrocytic membrane transporters and channels has revealed that aquaporin-4 (AQP4) and Kir4.1 potassium channels are concentrated in astrocytic membranes abutting blood vessels (Amiry-Moghaddam and Ottersen, 2003; Nagelhus et al., 1999; Nielsen et al., 1997) and demonstrated their roles in brain extracellular water and K + homeostasis (Amiry-Moghaddam et al., 2003; Haj-Yasein et al., 2011; Thrane et al., 2013) (Fig. 1C). We recently showed that loss of astrocyte polarity occurs in AD, epilepsy and stroke (Alvestad et al., 2013; Eid et al., 2005; Frydenlund et al., 2006; Heuser et al., 2012; Yang et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Glial cells in their plurality account for most of the mass of the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. Astrocyte biology has been examined using three-dimensional (3D) atomic and molecular structural methods, as well as 3D brain imaging in live animals and humans. Exosomes are extracelluar membrane vesicles that facilitate communication between glia, and have significant potential for biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may indirectly influence the structure and function of membrane proteins expressed in glial cells and predispose specific population subgroups to astro-and neurodegeneration. Physical exercise may reduce or retard age-related brain deterioration by a mechanism involving neuro-glial processes. It is most likely that more information about the distribution, structure and function of glial cells will yield novel insight into human brain ageing. Systematic studies of glia and their functions are expected to eventually lead to earlier detection of ageing-related brain dysfunction and to interventions that could delay, reduce or prevent brain dysfunction.
    Mechanisms of ageing and development 10/2013; 134(10). DOI:10.1016/j.mad.2013.10.001 · 3.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aquaporin-4 (AQP4) is one of the most abundant molecules in the brain and is particularly prevalent in astrocytic membranes at the blood-brain and brain-liquor interfaces. While AQP4 has been implicated in a number of pathophysiological processes, its role in brain physiology has remained elusive. Only recently has evidence accumulated to suggest that AQP4 is involved in such diverse functions as regulation of extracellular space volume, potassium buffering, cerebrospinal fluid circulation, interstitial fluid resorption, waste clearance, neuroinflammation, osmosensation, cell migration, and Ca(2+) signaling. AQP4 is also required for normal function of the retina, inner ear, and olfactory system. A review will be provided of the physiological roles of AQP4 in brain and of the growing list of data that emphasize the polarized nature of astrocytes.
    Physiological Reviews 10/2013; 93(4):1543-62. DOI:10.1152/physrev.00011.2013 · 27.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The nicotinamide adenine dinucleotide (NAD) derivatives NADH and NADPH are critical components of cellular energy metabolism and operate as electron carriers. A novel fluorescent ubiquinone-rhodol derivative (UQ-Rh) was developed as a probe for NAD(P)H. By using the artificial promoter [(η5-C5Me5)Ir(phen)(H2O)]2+, intracellular activation and imaging of NAD(P)H were successfully demonstrated. In contrast to bioorthogonal chemistry, this “bioparallel chemistry” approach involves interactions with native biological processes and could potentially be used to control or investigate cellular systems.
    Angewandte Chemie International Edition 04/2014; 53(15). DOI:10.1002/anie.201311192 · 11.26 Impact Factor
Show more