Developmentally regulated expression of CaMKII and iGluRs in the rat retina

Xue, Jin; Li, Guangyu; Bharucha, Eric; Cooper, Nigel G. F.

doi:10.1016/s0165-3806(02)00460-1

Cited by 13 publications

(19 citation statements)

References 66 publications

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“…We previously showed a genetic rescue of the major phenotypes in the AS mouse model using a specific mutation to alpha CaMKII [16]. Temporal regulation of alpha CaMKII expression results in little expression prior to post natal day 5 followed by increased expression to maximal levels by post natal day 21 [26]. The lack of appreciable CaMKII expression during development of the central nervous system suggested that CaMKII's effect was altering synaptic function resulting in the phenotype rescue.…”

Section: Discussionmentioning

confidence: 99%

Adeno-Associated Virus-Mediated Rescue of the Cognitive Defects in a Mouse Model for Angelman Syndrome

et al. 2011

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Angelman syndrome (AS), a genetic disorder occurring in approximately one in every 15,000 births, is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve abnormalities in brain structure, no gross anatomical changes are associated with AS. However, we have determined that abnormal calcium/calmodulin-dependent protein kinase II (CaMKII) regulation is seen in the maternal UBE3A deletion AS mouse model and is responsible for the major phenotypes. Specifically, there is an increased αCaMKII phosphorylation at the autophosphorylation sites Thr286 and Thr305/306, resulting in an overall decrease in CaMKII activity. CaMKII is not produced until after birth, indicating that the deficits associated with AS are not the result of developmental abnormalities. The present studies are focused on exploring the potential to rescue the learning and memory deficits in the adult AS mouse model through the use of an adeno-associated virus (AAV) vector to increase neuronal UBE3A expression. These studies show that increasing the levels of E6-AP in the brain using an exogenous vector can improve the cognitive deficits associated with AS. Specifically, the associative learning deficit was ameliorated in the treated AS mice compared to the control AS mice, indicating that therapeutic intervention may be possible in older AS patients.

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Section: Discussionmentioning

confidence: 99%

Adeno-Associated Virus-Mediated Rescue of the Cognitive Defects in a Mouse Model for Angelman Syndrome

et al. 2011

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“…The first evidence for a developmental regulated plasticity of glutamate receptors also in the retina was given by Xue and colleagues (24,25).…”

mentioning

confidence: 99%

Developmental plasticity of NMDA receptor function in the retina and the influence of light

Guenther¹,

Schmid²,

Wheeler‐Schilling³

et al. 2004

FASEB j.

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Despite the early expression of NMDA receptors (NMDARs) in the retina, not much is known about their regulation and involvement in plasticity processes during retinal development and synapse formation. Here we report that NMDAR function in the inner retina is developmentally regulated and controlled by ambient light condition. A prominent down-regulation after eye opening of NMDAR function was observed in rat retinal ganglion cells (RGCs), which was prevented by dark rearing the animals for 1 month but was again induced by subsequent light exposure. As shown by molecular analysis of single RGCs, alterations in the subunit composition of NMDAR did not account for the light-dependent regulation of NMDAR function. Immunocytochemistry showed no differences in the NMDAR protein expression pattern between normal and dark-reared animals. In conclusion, our data clearly demonstrate that NMDAR function is modulated during periods of retinal plasticity independent of structural alterations in its subunit composition and thus different from mechanisms observed in higher visual centers.

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“…Previous experiments by Guenther et al [41] have shown a developmental shortening of the NMDAR-mediated currents in rat retina, similar to that in visual cortex, [36] while they have shown that the NR2A/NR2B ratio within a single retinal ganglion cell was not developmentally altered. In contrast, Xue et al [28] have shown a progressive inclusion of NR2A subunit over the course of development.…”

Section: Discussionmentioning

confidence: 79%

“…Furthermore, distinct bands of immunoreactivity are observed from P14 in the inner plexiform layer (IPL) and a weak labelling in the outer plexiform layer (OPL) late in development [23,24]. Xue et al [28] have indicated by immunoblotting that NR1 levels increase steadily during the first three postnatal weeks. Alternative splicing of the NR1 subunit mRNA has been examined in rat brain [29,30] and in response to optic nerve crush in the retina [21].…”

Section: Introductionmentioning

confidence: 99%

“…During retinal development, shortening of the NMDAR-mediated currents is observed in rat RGCs and this event is prevented by dark rearing the animals for 1 month [41]. Furthermore, modifications of retinal NMDAR subunit expression are observed during development and by dark rearing [28,[41][42][43]. In addition, visual experience regulates the development of retinal circuitry itself.…”

Section: Introductionmentioning

confidence: 99%

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Age and Visual Experience-dependent Expression of NMDAR1 Splice Variants in Rat Retina

et al. 2011

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The N-methyl-D-aspartate receptor (NMDAR) is a key molecule mediating brain plasticity related processes. Knowing that alternative splicing of the NMDAR1 (NR1) subunit offers molecular diversity to NMDAR, controls the forward trafficking of the NR1 protein and is important for placing NMDA receptors at synapses, we investigated herein the postnatal developmental expression and the influence of visual deprivation on NR1 subunit splice variants in rat retina. Real-time PCR was performed using oligonucleotide primers specific for N- terminal (NR1a, NR1b) and C-terminal splice variants (NR1-1, NR1-2, NR1-3, NR1-4). The developmental profiles of mRNA expression levels of all NR1 isoforms peaked at the end of the third week. Dark rearing led to reductions in both N- and C-terminal NR1 variants in several developmental ages and a significant interaction between age and visual experience was observed for NR1a, NR1-2 and NR1-4 expression. Our results have demonstrated a developmental and visual experience-dependent regulation of NR1 splicing in rat retina.

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Developmentally regulated expression of CaMKII and iGluRs in the rat retina

Cited by 13 publications

References 66 publications

Adeno-Associated Virus-Mediated Rescue of the Cognitive Defects in a Mouse Model for Angelman Syndrome

Adeno-Associated Virus-Mediated Rescue of the Cognitive Defects in a Mouse Model for Angelman Syndrome

Developmental plasticity of NMDA receptor function in the retina and the influence of light

Age and Visual Experience-dependent Expression of NMDAR1 Splice Variants in Rat Retina

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