The developmental and aging changes of Down's syndrome cell adhesion molecule expression in normal and Down's syndrome brains

Saito, Yoshiaki; Oka, Akira; Mizuguchi, Masashi; Motonaga, Kozo; Mori, Yuji; Becker, Laurence E.; Arima, Kunimasa; Miyauchi, Jun; Takashima, Sachio

doi:10.1007/s004010000230

Cited by 54 publications

(51 citation statements)

References 33 publications

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“…Increased DSCAM protein levels in the brains of DS patients have been reported (Saito et al, 2000). We observed that overexpression of DSCAM in hippocampal neurons produced a dramatic inhibition of dendrite branching, in agreement with the dendritic phenotype observed in DS patients (Marin-Padilla, 1972).…”

Section: Discussionsupporting

confidence: 89%

NMDA-Mediated Regulation ofDSCAMDendritic Local Translation Is Lost in a Mouse Model of Down's Syndrome

Alves-Sampaio¹,

Troca-Marín²,

Montesinos³

2010

J. Neurosci.

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Down's syndrome cell adhesion molecule (DSCAM) belongs to the Down's syndrome critical region of human chromosome 21, and it encodes a cell adhesion molecule involved in dendrite morphology and neuronal wiring. Although the function of DSCAM in the adult brain is unknown, its expression pattern suggests a role in synaptic plasticity. Local mRNA translation is a key process in axonal growth, dendritogenesis, and synaptogenesis during development, and in synaptic plasticity in adulthood. Here, we report the dendritic localization of DSCAM mRNA in the adult mouse hippocampus, where it associates with CPEB1 [cytoplasmic polyadenylation element (CPE) binding protein 1], an important regulator of mRNA transport and local translation. We identified five DSCAM isoforms produced by alternative polyadenylation bearing different combinations of regulatory CPE motifs. Overexpression of DSCAM in hippocampal neurons inhibited dendritic branching. Interestingly, dendritic levels of DSCAM mRNA and protein were increased in hippocampal neurons from Ts1Cje mice, a model of Down's syndrome. Most importantly, DSCAM dendritic translation was rapidly induced by NMDA in wild-type, but not in Ts1Cje neurons. We propose that impairment of the NMDA-mediated regulation of DSCAM translation may contribute to the alterations in dendritic morphology and/or synaptic plasticity in Down's syndrome.

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Section: Discussionsupporting

confidence: 89%

NMDA-Mediated Regulation ofDSCAMDendritic Local Translation Is Lost in a Mouse Model of Down's Syndrome

Alves-Sampaio¹,

Troca-Marín²,

Montesinos³

2010

J. Neurosci.

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“…4). This expression pattern, which is very similar to that described for DSCAM in the human adult brain using immunohistochemistry (Saito et al, 2000), is of significance as these regions of the brain are involved in the input and processing of somatosensory information, spatial and explicit learning and memory, and the learning of motor skills (Kandel et al, 1995). Moreover, the cortex, hippocampus and cerebellum are particularly affected in DS (Becker et al, 1993;Jernigan et al, 1993;Golden and Hyman, 1994).…”

Section: Pattern Of Dscam Expression In the Adult Brainsupporting

confidence: 66%

Down Syndrome Cell Adhesion Molecule is conserved in mouse and highly expressed in the adult mouse brain

Micales¹,

Lyons²,

Korenberg

2001

Cytogenet Genome Res

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Down Syndrome (DS) is a major cause of mental retardation and is associated with characteristic well-defined although subtle brain abnormalities, many of which arise after birth, with particular defects in the cortex, hippocampus and cerebellum. The neural cell adhesion molecule DSCAM (Down syndrome cell adhesion molecule) maps to 21q22.2→q22.3, a region associated with DS mental retardation, and is expressed largely in the neurons of the central and peripheral nervous systems during development. In order to evaluate the contribution of DSCAM to postnatal morphogenetic and cognitive processes, we have analyzed the expression of the mouse DSCAM homolog, Dscam, in the adult mouse brain from 1 through 21 months of age. We have found that Dscam is widely expressed in the brain throughout adult life, with strongest levels in the cortex, the mitral and granular layers of the olfactory bulb, the granule cells of the dentate gyrus and the pyramidal cells of the CA1, CA2 and CA3 regions, the ventroposterior lateral nuclei of the thalamus, and in the Purkinje cells of the cerebellum. Dscam is also expressed ventrally in the adult spinal cord. Given the homology of DSCAM to cell adhesion molecules involved in development and synaptic plasticity, and its demonstrated role in axon guidance, we propose that DSCAM overexpression contributes not only to the structural defects seen in these regions of the DS brain, but also to the defects of learning and memory seen in adults with DS.

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“…Compared with the normal subjects, the patients with DS have increased cerebral expression of DSCAM protein because of the trisomy of chromosome 21. Elevated levels of DSCAM protein may lead to abnormal lamination and gross architecture through alterations of the adhesive properties of neurons (Agarwala et al, 2000;Saito et al, 2000). Given the homology of DSCAM to cell adhesion molecules involved in development and synaptic plasticity, we speculated that Dscam gene to be the best candidate for a putative signal in affecting SGZ progenitor cell fate.…”

Section: Figurementioning

confidence: 99%

Implication of “Down syndrome cell adhesion molecule” in the hippocampal neurogenesis of ischemic monkeys

et al. 2006

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Molecular signals regulating adult neurogenesis in primates are largely unknown. Here the authors used differential display to analyze gene expression changes that occur in dentate gyrus of adult monkeys after transient global cerebral ischemia. Among 14 genes upregulated, the authors focused on Down syndrome cell adhesion molecule (DSCAM) known to play crucial role during neuronal development, and characterized its expression pattern at the protein level. In contrast with approximately threefold upregulation of Dscam gene on days 5 and 7, immunoblotting and immunofluorescence analyses using specific antibodies showed a gradual decrease of DSCAM after ischemia until day 9 followed by recovery on day 15. In the control, immunofluorescence reactivity of DSCAM was detected in dentate gyrus granule cells and CA4 neurons but decreased after ischemia, being compatible with the immunoblotting data. However, in the subgranular zone, cerebral ischemia led to a marked increase of DSCAM-positive cells on days 9 and 15. DSCAM upregulation was seen in two cell types: one is immature neurons positive for polysialylated neural cell adhesion molecule or betaIII-tubulin, while another is astrocytes positive for S100beta. Young astrocytes were in intimate contact with newly generated neurons in the subgranular zone. These data suggest implication of DSCAM in the adult neurogenesis of primate hippocampus upregulated after ischemia.

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The developmental and aging changes of Down's syndrome cell adhesion molecule expression in normal and Down's syndrome brains

Cited by 54 publications

References 33 publications

NMDA-Mediated Regulation ofDSCAMDendritic Local Translation Is Lost in a Mouse Model of Down's Syndrome

NMDA-Mediated Regulation ofDSCAMDendritic Local Translation Is Lost in a Mouse Model of Down's Syndrome

Down Syndrome Cell Adhesion Molecule is conserved in mouse and highly expressed in the adult mouse brain

Implication of “Down syndrome cell adhesion molecule” in the hippocampal neurogenesis of ischemic monkeys

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