Localization of dystrophin to postsynaptic regions of central nervous system cortical neurons

The dystrophin gene and cognitive function in the general population

“…It has been shown that this form of protein dystrophin colocalizes with inhibitory GABA receptor clusters at the postsynaptic membranes of hippocampal and neocortical pyramidal neurons where the synapse function is modulated. [45][46][47][48] According to various studies this dystrophin isoform has a stabilizing effect on the GABA receptors by limiting their lateral diffusion outside the synapse. 49,50 Importance of GABA receptors for the regulation of cognition, emotion and memory is increasingly being recognized.…”

Selective deficits in verbal working memory associated with a known genetic etiology: The neuropsychological profile of Duchenne muscular dystrophy

“…Dystrophin products localized to neurons are only found in the soma and dendrites (not the axon) and tend to aggregate at the postsynaptic densities, suggesting a possible role in synaptic function (Dorbani-Mamine et al, 1998;Jancsik & Hajos, 1998;Kim et al, 1992;Lidov et al, 1990;Uchino et al, 1994a). Further, dystrophin products in the central nervous system are found more in the cerebral and cerebellar cortices than in lower brain structures (Gorecki et al, 1998(Gorecki et al, ,1992Kimura et al, 1997;Lidov et al, 1990;Tian et al, 1996;Uchino et al, 1994a,b), and various theories of the neuroanatomical basis of working memory and/or attention have localized these abilities to cortical areas (Baddeley, 1986;Goldman-Rakic, 1988;Mesulam, 1990;Posner & Peterson, 1990). Future neurobiological work examining the role of dystrophin in the development of the brain may offer greater insight into the neurological basis of verbal working memory.…”

“…In human DMD autopsy tissue and in mouse models of DMD, no brain dystrophin has been found. In normal brain tissue, however, different forms of brain dystrophin have been localized both to specific cell types, as well as to specific brain regions (Gorecki et al, 1992(Gorecki et al, ,1998Kimura et al, 1997;Lidov et al, 1990;Tian et al, 1996;Uchino et al, 1994a,b). One type is localized specifically to the pyramidal cells of the cerebral cortex and the hippocampus, and does not appear to localize to lower brain structures.…”

Efficient repetitive gene delivery to skeletal muscle using recombinant adenovirus vector containing the Coxsackievirus and adenovirus receptor cDNA

“…Serial sections from antero-tibialis muscles inoculated with AdCMVhCAR-LacZ and AdRSVEGFP, AdCMVLacZ and AdRSVEGFP, or not treated, were stained with three first antibodies: anti-hCAR antibody, 24 anti-dystrophin antibody, 25 or anti-␤-dystroglycan antibody, respectively ( Figure 4). The hCAR was located on plasma membranes of many muscle fibers infected with AdCMVhCAR-LacZ (Figure 4b and p).…”

“…For using mouse monoclonal antibodies, especially for adding, the slides were further blocked with Super block reagent (ScyTeK, West Logan, UT, USA) for 5 min and with Mouse to Mouse block reagent (ScyTeK) in TPBS at room temperature for 15 min and washed with PBS four times. They were then incubated with anti-human CAR rabbit polyclonal antibody 24 (anti-CAR, donated by Dr GE Blair (School of Biochemistry and Molecular Biology, University of Leeds, UK), 1:200 diluted with TPBS), or anti-dystrophin rabbit polyclonal antibody 25 (anti-6-10 antibody, donated by TJ Byers and LM Kunkel (Department of Medicine (Genetics), Howard Hughes Medical Institute, Children's Hospital, Boston, MA, USA), 1:1000), or anti-␤-dystroglycan monoclonal antibody (NCL-43DAG; Novacastra Laboratories, Newcastle upon Tyne, UK, 1:50) at room temperature for 2 h. After washing carefully with TPBS three times for 10 min each, sections were incubated with Cy3-conjugated antirabbit donkey second antibody (Jackson ImmunoResearch Laboratories, West Grove, PA, USA, 1:500 diluted with TPBS) or Cy3-conjugated anti-mouse goat second antibody (Jackson ImmunoResearch Laboratories, 1:500 diluted with TPBS), respectively, at room temperature for 2 h in a dark room, and then washed carefully with TPBS three times. They were then mounted and observed with a Confocal Laser Scan Microscope (LSM410; Carl Zeiss Microscopy).…”