Subcellular localization of Dp71 dystrophin isoforms in cultured hippocampal neurons and forebrain astrocytes

Aleman, Victor; Osorio, Beatriz; Chávez, O scar; Rendón, Álvaro; Mornet, Dominique; Martinez, D. A.

doi:10.1007/s004180000221

Cited by 40 publications

(21 citation statements)

References 36 publications

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“…Thus, the clustered and polarized distribution of Kir4.1 channels may play a analogous role in astrocytes in brain as that of Müller cells in retina. Relevant to our findings, Dp71 is also expressed in astrocytes in brain (Aleman et al, 2001). Marked neurological dysfunctions for the mouse line mdx 3Cv has not been reported, but it is likely that a perturbation in the potassium buffering function in brain would only manifest under conditions of high neuronal activity.…”

Section: Discussionsupporting

confidence: 89%

Dystrophin Dp71 Is Critical for the Clustered Localization of Potassium Channels in Retinal Glial Cells

2002

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The Müller cell is the principal glial cell of the vertebrate retina. The primary conductance in Müller cells is the inwardly rectifying potassium channel Kir4.1 (BIR10 and KAB-2), which is highly concentrated at the endfeet at the vitreal border and to processes enveloping blood vessels. Such asymmetric and clustered distribution of Kir4.1 channels in Müller cells is thought to be critical for the buffering of extracellular potassium concentration in retina. Herein we investigated whether the distribution and functional properties of Kir4.1 channels are dependent on expression of the Dp71, a dystrophin isoform expressed in Müller cells. Kir4.1 distribution was determined in mouse retinal sections and whole mounts using anti-Kir4.1 antibodies and confocal microscopy. In Müller cells from wild-type mice, Kir4.1 is highly clustered in their endfeet and perivascular processes. In contrast, in Müller cells from the mdx(3Cv) mouse, which lacks the expression of Dp71, the Kir4.1 immunoreactivity is evenly distributed throughout the cell membrane. Surface expression of Kir4.1 is not affected in mdx(3Cv) Müller cells as current density of barium-sensitive inward currents in mdx(3Cv) Müller cells are not different from wild type. Focal extracellular potassium increases in isolated Müller cells shows that Kir channels in the mdx(3Cv) cells, as opposed to wild type, are less prominently concentrated in their endfeet. In summary, our data indicate that Dp71 is critical for the clustering but not membrane expression of Kir4.1 in mouse Müller cells. These results point to a new role for dystrophin in glial cells.

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Section: Discussionsupporting

confidence: 89%

Dystrophin Dp71 Is Critical for the Clustered Localization of Potassium Channels in Retinal Glial Cells

2002

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“…Neuropathological studies have demonstrated that dystrophin isoforms are missing from hippocampal areas. 22,23 Additionally, hippocampal brain slices from the mdx mouse (a model for DMD) have been shown to have reduced functional capacity in some situations. 24 Vailliend et al 25 have offered evidence that longterm potentiation associated with learning is disrupted in the mdx mouse, affecting memory consolidation.…”

Section: Discussionmentioning

confidence: 99%

Verbal and memory skills in males with Duchenne muscular dystrophy

Hinton

Fee

Goldstein

et al. 2007

Develop Med Child Neuro

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Duchenne muscular dystrophy (DMD) is a progressive pediatric disorder that affects both muscle and brain. Children with DMD have mean IQ scores that are about one standard deviation lower than population means, with lower Verbal IQ than Performance IQ scores. For the present study, verbal skills and verbal memory skills were examined in males with DMD with the Clinical Evaluation of Language Fundamentals, 3rd edition, and the California Verbal Learning Test for Children. Performance of 50 males with DMD (age range 6-14y, mean 9y 4mo [SD 2y 1mo]) was compared to normative values. Two subsets of the probands were also compared with two comparison groups: unaffected siblings (n=24; DMD group age range 6-12y, mean 9y 1mo [SD 1y 8mo]; sibling age range 6-15y, mean 9y 11mo [SD 2y 4mo]) and males with cerebral palsy (CP);(n=23; DMD group age range 6-9y, mean 7y 8mo [SD 1y 2mo]; CP age range 6-8y, mean 6y 8mo [SD 0y 8mo]). Results demonstrated that although males with DMD performed slightly more poorly than normative values, they performed comparably to the controls on most measures. Consistent deficits were observed only on tests requiring immediate repetition for verbal material (Recalling Sentences, and Concepts and Directions). On other language tasks, including tests of understanding and use of grammar, and understanding of semantic relationships, the males with DMD performed well. Moreover, the males with DMD performed well on multiple indices of verbal recall, and there was no evidence of declarative memory deficits. DMD is a single-gene disorder that is selectively associated with decreased verbal span capacity, but not impaired recall.The cognitive presentation in Duchenne muscular dystrophy (DMD) is intriguing. Ever since its original characterization by Duchenne, 1 the illness has been known to be associated with 'dull' intellect and 'difficult' speech in some affected individuals, yet most do not have significant cognitive complaints. DMD presents with progressive physical disability and a shortened lifespan. DMD is primarily a disease of muscle, yet it also affects the central nervous system. Individuals with DMD have a genetic mutation that prevents the production of the protein product dystrophin, and of multiple dystrophin isoforms. In muscle, lack of dystrophin results in unstable muscle cell membranes that break down over time, causing progressive weakness. In the brain, a lack of dystrophin isoforms has been documented in the cerebral cortex and cerebellum, in specific cell types (especially pyramidal and Purkinje cells) and in specific cell areas (especially the neuronal postsynaptic densities). 2,3 As a group, children with DMD present with relatively weak verbal and immediate memory skills. [4][5][6][7][8] There is individual variation across factors that contribute to the cognitive phenotype, including intellectual level, age, degree of physical disability, and background environment. The goal of the present study was to explore, in detail, language and verbal memory skills in children with DMD.A...

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“…Dystrophin 71 (Dp71), a membrane-associated cytoskeletal protein and one of the smaller Duchenne muscular dystrophy (DMD) gene products that is the core of the Dystrophin-Associated Protein (DAP) complex, links the intracellular actin cytoskeleton to the extracellular matrix. Studies on nervous tissue support the potential involvement of Dp71 in neuronal and glial cell functions (Aleman et al, 2001;Claudepierre et al, 2000;Dalloz et al, 2003;Daoud et al, 2009;Fort et al, 2008). Dp71 mRNA and protein have been shown to be expressed in different brain structures and cell types, including perivascular astrocytes, neurons in the hippocampus and olfactory bulb, cultured hippocampal neurons and forebrain astrocytes, and postsynaptic densities in vivo.…”

Section: Introductionmentioning

confidence: 94%

Altered astrocyte morphology and vascular development in dystrophin‐Dp71‐null mice

Giocanti-Aurégan

Vacca

Bénard

et al. 2015

Glia

Self Cite

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Understanding retinal vascular development is crucial because many retinal vascular diseases such as diabetic retinopathy (in adults) or retinopathy of prematurity (in children) are among the leading causes of blindness. Given the localization of the protein Dp71 around the retinal vessels in adult mice and its role in maintaining retinal homeostasis, the aim of this study was to determine if Dp71 was involved in astrocyte and vascular development regulation. An experimental study in mouse retinas was conducted. Using a dual immunolabeling with antibodies to Dp71 and anti-GFAP for astrocytes on retinal sections and isolated astrocytes, it was found that Dp71 was expressed in wild-type (WT) mouse astrocytes from early developmental stages to adult stage. In Dp71-null mice, a reduction in GFAP-immunopositive astrocytes was observed as early as postnatal day 6 (P6) compared with WT mice. Using real-time PCR, it was showed that Dp71 mRNA was stable between P1 and P6, in parallel with post-natal vascular development. Regarding morphology in Dp71-null and WT mice, a significant decrease in overall astrocyte process number in Dp71-null retinas at P6 to adult age was found. Using fluorescence-conjugated isolectin Griffonia simplicifolia on whole mount retinas, subsequent delay of developing vascular network at the same age in Dp71-null mice was found. An evidence that the Dystrophin Dp71, a membrane-associated cytoskeletal protein and one of the smaller Duchenne muscular dystrophy gene products, regulates astrocyte morphology and density and is associated with subsequent normal blood vessel development was provided.

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Subcellular localization of Dp71 dystrophin isoforms in cultured hippocampal neurons and forebrain astrocytes

Cited by 40 publications

References 36 publications

Dystrophin Dp71 Is Critical for the Clustered Localization of Potassium Channels in Retinal Glial Cells

Dystrophin Dp71 Is Critical for the Clustered Localization of Potassium Channels in Retinal Glial Cells

Verbal and memory skills in males with Duchenne muscular dystrophy

Altered astrocyte morphology and vascular development in dystrophin‐Dp71‐null mice

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