Ultrastructural Localization of Aquaporin 4 and .ALPHA.1-Syntrophin in the Vascular Feet of Brain Astrocytes.

Inoue, Masahiko; Wakayama, Yoshihiro; Liu, Jian Wu; Murahashi, Makoto; Shibuya, Seiji; Oniki, Hiroaki

doi:10.1620/tjem.197.87

Cited by 25 publications

(22 citation statements)

References 11 publications

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“…This suggestion was further substantiated by recent studies of brain microvessels in mdx mice (Inoue et al 2002;Nico et al 2003Nico et al , 2004, showing that both endothelial and glial cells were altered, suggesting changes in vascular permeability, i.e., breakdown of the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 64%

Immunofluorescence mapping of dystrophin in the rat brain: astrocytes contain the splice variant Dp71f, but this is confined to subpopulations

et al. 2004

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Dystrophins are membrane-associated actin-binding proteins, recognized at first in muscular dystrophies. In the brain the full-length Dp427 has been detected, as well as Dp140 and Dp71 of the shorter variants. Dp71 seems to be their major representative in the brain, and it occurs as splice variants, Dp71f and Dp71d. Dystrophins have been demonstrated mainly in neurons. In tissue cultures, the glial data, mainly in situ, are still insufficient. The present mapping study reveals the astroglial localization of the splice variant Dp71f, using a monoclonal antibody (5F3, developed by D. Mornet) specific for its additional 31 last amino acids. In parallel, another monoclonal antibody was used (Dys2, Novocastra) that detects the Dp71d, Dp427, as well as Dp140 and other short variants. Rats were overdosed with ether and perfused transcardially with 4% phosphate-buffered paraformaldehyde solution. Floating Vibratome sections were processed for immunohistochemical labeling with fluorescent secondary antibodies. In some animals the reactive glia were investigated following stab wounds in ketamine-xylazine anesthesia. Only the 5F3 antibody labeled astrocytes, however, not in general but in special localizations, mainly along the glia limitans of the pial surface, below the ependyma and in the reactive glia. Perivascular astrocytes were consistently labeled only where the vessels entered the brain, and in some circumventricular organs. The 5F3 antibody also labeled the ependyma and the residual subventricular zone. In contrast to the astrocytes, neurons were labeled throughout the brain. Dys2 antibody (to Dp71d and longer isoforms) labeled neurons in a distribution similar to that of 5F3, but rarely labeled astroglia and only in perivascular rings. Dp71f positivity seems to occur in those astrocyte populations that proved to be immunopositive to glial fibrillary acidic protein (GFAP) and produced laminin in former studies.

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Section: Discussionmentioning

confidence: 64%

Immunofluorescence mapping of dystrophin in the rat brain: astrocytes contain the splice variant Dp71f, but this is confined to subpopulations

et al. 2004

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“…These two channels plus a-syntrophin and other DGC members also aggregate in glia when presented with laminin in cell culture (Guadagno and Moukhles, 2004). In addition, immunolocalization studies have shown that Kir4.1 and AQP4 are tightly co-localized in rat retina (Nagelhus et al, 1999), and AQP4 localization in astrocytes appears to be highly dependent on a-syntroin (Inoue et al, 2002). Direct interactions between AQP4, a-syntrophin, Dp71 and b-dystroglycan have been shown by IP assays (Neely et al, 2001;Amiry-Moghaddam et al, 2003a,b).…”

Section: Discussionmentioning

confidence: 98%

Potassium channel Kir4.1 macromolecular complex in retinal glial cells

Connors

Kofuji

2005

Glia

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“…In the brain, they are mainly expressed in perivascular astrocytes and in choroid plexuses, suggesting a potential role in water homeostasis, regulation of transport mechanisms across BBB and cerebrospinal fluid production. 7,10,19,31,39,44 Mutations of DAPs are involved in muscular dystrophy, 45 and are responsible for structural and biochemical changes in the brain. 46 The dystrophin isoform Dp71 is localized in the perivascular glial endfeet, in which it is involved in BBB maturation 39,47 and in the clustering of the AQP4 water channel on the astrocyte glial membranes.…”

Section: Discussionmentioning

confidence: 99%

Glial dystrophin-associated proteins, laminin and agrin, are downregulated in the brain of mdx mouse

Nico

Tamma

Annese

et al. 2010

Laboratory Investigation

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In this study, we investigated the involvement of dystrophin-associated proteins (DAPs) and their relationship with the perivascular basement membrane in the brains of mdx mice and controls at the age of 2 months. We analyzed (1) the expression of glial DAPs a-b-dystroglycan (DG), a-syntrophin, aquaporin-4 (AQP4) water channel, Kir 4.1 and dystrophin isoform (Dp71) by immunocytochemistry, laser confocal microscopy, immunogold electron microscopy, immunoblotting and RT-PCR; (2) the ultrastructure of the basement membrane and expression of laminin and agrin; and (3) the dual immunofluorescence colocalization of AQP4/a-b-DG, and of Kir 4.1/agrin. The following results were observed in mdx brain as compared with controls: (1) a significant reduction in protein content and mRNA expression of DAPs; (2) ultrastructurally, a thickened and discontinuous appearance of the basement membrane and a significant reduction in laminin and agrin; and (3) a molecular rearrangment of a-b-DG, coupled with a parallel loss of agrin and Kir 4.1 on basement membrane and glial endfeet. These data indicate that in mdx brain the deficiency in dystrophin and dystrophin isoform (Dp71) is coupled with a reduction of DAP components, coupled with an altered anchoring to the basement membrane. The blood-brain barrier (BBB) controls the selective exchanges between blood and neuropil by specific molecular and structural features of its vascular and perivascular components, including endothelial cells, pericytes, glial endfeet and basement membrane. 1-3 Glial cells have a key role in the control of BBB development and integrity. They express in a polarized way, on their perivascular endfeet, carrier membranes and channel proteins, including aquaporin-4 (AQP4) water channel and potassium channel Kir 4.1, which are responsible for the water flow rate and spatial K þ buffering control. [4][5][6][7][8][9] In the retina, AQP4 colocalizes with Kir 4.1, 9-11 suggesting a tight cooperation between the water flux and K þ siphoning generated by neuronal activity at the BBB interfaces. Moreover, AQP4 and Kir 4.1 rearrangement has been described in BBB alterations, coupled with cytotoxic edema and K þ -delayed buffering capacity. 12,13 AQP4 has a crucial role in the regulation of the interactions occurring between endothelial and glial cells and between glial cells and the extracellular matrix components. AQP4 is a component of the orthogonal aggregate particles (OAPs), demonstrated by freeze fracturing on the ependimoglial membrane and perivascular glial endfeet, 14 the development of which occurs in parallel with AQP4 glial endfeet expression and BBB maturation. 7 Moreover, OAPs contain AQP4 associated with Kir 4.1 12 and their polarized distribution on the glial endfeet seems to be dependent by the presence of the perivascular basement membrane. 15 AQP4 controls BBB functioning, modifying

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Ultrastructural Localization of Aquaporin 4 and .ALPHA.1-Syntrophin in the Vascular Feet of Brain Astrocytes.

Cited by 25 publications

References 11 publications

Immunofluorescence mapping of dystrophin in the rat brain: astrocytes contain the splice variant Dp71f, but this is confined to subpopulations

Immunofluorescence mapping of dystrophin in the rat brain: astrocytes contain the splice variant Dp71f, but this is confined to subpopulations

Potassium channel Kir4.1 macromolecular complex in retinal glial cells

Glial dystrophin-associated proteins, laminin and agrin, are downregulated in the brain of mdx mouse

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