Postadolescent Changes in Regional Cerebral Protein Synthesis: An<i>In Vivo</i>Study in the<i>Fmr1</i>Null Mouse

Qin, Mei; Kang, Julia; Burlin, Thomas V; Jiang, Chunhui; Smith, Carolyn Beebe

doi:10.1523/jneurosci.0093-05.2005

Cited by 236 publications

(235 citation statements)

References 47 publications

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“…Since FMRP is thought to repress protein synthesis (Laggerbauer, Ostareck et al 2001;Li, Zhang et al 2001), a loss of function mutation of the FMR1 allele is expected to enhance protein synthesis of FMRPrepressed proteins. Consistent with this view, radiotracer autoradiography indicates enhanced protein expression in hypothalamus, thalamus, basolateral amygdala, hippocampus, frontal association, and posterior parietal cortex of FMR1 knockout mice (Qin, Kang et al 2005). …”

Section: Fragile X Mousementioning

confidence: 71%

The cyclic AMP phenotype of fragile X and autism

Kelley

Bhattacharyya

Lahvis

et al. 2008

Neuroscience & Biobehavioral Reviews

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Cyclic AMP (cAMP) is a second messenger involved in many processes including mnemonic processing and anxiety. Memory deficits and anxiety are noted in the phenotype of fragile X (FX), the most common heritable cause of mental retardation and autism. Here we review reported observations of altered cAMP cascade function in FX and autism. Cyclic AMP is a potentially useful biochemical marker to distinguish autism comorbid with FX from autism per se and the cAMP cascade may be a viable therapeutic target for both FX and autism.

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Section: Fragile X Mousementioning

confidence: 71%

The cyclic AMP phenotype of fragile X and autism

Kelley

Bhattacharyya

Lahvis

et al. 2008

Neuroscience & Biobehavioral Reviews

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“…Even relatively small errors in rCPS are problematic because effects of different conditions and disease states on rCPS are not expected to be large. On the basis of our experience in rodent experiments with the L-[1-14 C]leucine autoradiographic method, most effects on rCPS are < 20% (Smith, 1991;Qin et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Use of Acute Hyperphenylalaninemia in Rhesus Monkeys to Examine Sensitivity and Stability of the l-[1-¹¹C]Leucine Method for Measurement of Regional Rates of Cerebral Protein Synthesis with Pet

Smith

Schmidt

Bishu

et al. 2008

J Cereb Blood Flow Metab

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We have previously shown by direct comparison with autoradiographic and biochemical measurements that the L-[1-11 C]leucine positron emission tomography method provides accurate determinations of regional rates of cerebral protein synthesis (rCPS) and the fraction (k) of unlabeled leucine in the precursor pool for protein synthesis derived from arterial plasma. In this study, we examine sensitivity of the method to detect changes in k and stability of the method to measure rCPS in the face of these changes. We studied four isoflurane-anesthetized monkeys dynamically scanned with the high resolution research tomograph under control and mild hyperphenylalaninemic conditions. Hyperphenylalaninemia was produced by an infusion of phenylalanine that increased plasma phenylalanine concentrations three-to five-fold. In phenylalanine-infused monkeys, plasma leucine concentrations remained relatively constant, but values of k were statistically significantly decreased by 11% to 15%; rCPS was unaffected. Effects on k are consistent with competitive inhibition of leucine transport by increased plasma phenylalanine. The effect on k shows that competition for the transporter results in a reduction in the fraction of leucine in the precursor pool for protein synthesis coming from plasma. Even under these hyperphenylalaninemic conditions, rCPS remains unchanged due to the compensating increased contribution of leucine from protein degradation to the precursor pool.

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“…A widespread increase in the rate of basal protein synthesis has been reported in KO mice, using both direct measurement of incorporation of radioactive precursors into protein in vivo (Qin et al, 2005) and indirect estimates based on mRNA granule peaks on sucrose gradients (Aschrafi et al, 2005). This increased ongoing protein synthesis (and turnover) may account for another phenotype that has been observed in visual cortex, the increased density (by about 20%), and length of dendritic spines (McKinney et al, 2005).…”

Section: Cortical Plasticity In the Mouse Model Of Fxsmentioning

confidence: 96%

Fragile X: Translation in Action

Bear

Dölen

Osterweil

et al. 2007

Neuropsychopharmacol

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Fragile X is a synapsopathy-a disorder of synaptic function and plasticity. Recent studies using mouse models of the disease suggest that the critical defect is altered regulation of synaptic protein synthesis. Various strategies to restore balanced synaptic protein synthesis have been remarkably successful in correcting widely varied mutant phenotypes in mice. Insights gained by the study of synaptic plasticity in animal models of fragile X have suggested novel therapeutic approaches, not only for human fragile X but also for autism and mental retardation of unknown etiology.

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Postadolescent Changes in Regional Cerebral Protein Synthesis: AnIn VivoStudy in theFmr1Null Mouse

Cited by 236 publications

References 47 publications

The cyclic AMP phenotype of fragile X and autism

The cyclic AMP phenotype of fragile X and autism

Use of Acute Hyperphenylalaninemia in Rhesus Monkeys to Examine Sensitivity and Stability of the l-[1-¹¹C]Leucine Method for Measurement of Regional Rates of Cerebral Protein Synthesis with Pet

Fragile X: Translation in Action

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Postadolescent Changes in Regional Cerebral Protein Synthesis: AnIn VivoStudy in theFmr1Null Mouse

Cited by 236 publications

References 47 publications

The cyclic AMP phenotype of fragile X and autism

The cyclic AMP phenotype of fragile X and autism

Use of Acute Hyperphenylalaninemia in Rhesus Monkeys to Examine Sensitivity and Stability of the l-[1-11C]Leucine Method for Measurement of Regional Rates of Cerebral Protein Synthesis with Pet

Fragile X: Translation in Action

Contact Info

Product

Resources

About

Use of Acute Hyperphenylalaninemia in Rhesus Monkeys to Examine Sensitivity and Stability of the l-[1-¹¹C]Leucine Method for Measurement of Regional Rates of Cerebral Protein Synthesis with Pet