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<title>Diminished rates of protein synthesis in a mouse model of Tuberous Sclerosis Complex: an mTORC1-dependent phenomenon | NIH Research Festival</title>
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<article><div class="banner banner--gray banner--compact" style="--banner-background-image: url('/sites/default/files/media/image/2021-03/2015.jpg');--banner-background-focus: 50% 50%"><div class="banner__wrapper"><div class="banner__container"><h2 class="banner__heading">NIH Research Festival</h2><div class="banner__content"><p><strong><time datetime="2015-09-16">September 16</time> – <time datetime="2015-09-18">18, 2015</time></strong></p></div></div></div></div></article>
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<div class="section"><div data-drupal-messages-fallback class="hidden"></div></div><main role="main"><div id="main-content" tabindex="-1"></div><div class="section"><div class="content-sidebar"><div class="content-sidebar__main"><div class="content-sidebar__main-content"><div id="block-mainpagecontent-2"><article><h1>Diminished rates of protein synthesis in a mouse model of Tuberous Sclerosis Complex: an mTORC1-dependent phenomenon</h1><div class="schedule"><div class="schedule__label"><div class="schedule__label-text"><time datetime="2015-09-18">Friday, September 18, 2015</time>
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– Poster Session V
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</div></div><div class="schedule__content"><div class="schedule__item"><div class="schedule__time">2:00 – 3:30 p.m.</div><div class="schedule__description"><p><strong>FAES Terrace</strong></p></div><div class="schedule__description"><p><strong>NIMH</strong></p></div><div class="schedule__description"><p><strong>NEURO-34</strong></p></div></div></div></div><h2>Authors</h2><ul><li>RM Reith</li><li>T Huang</li><li>T Burlin</li><li>C Beebe Smith</li></ul><h2>Abstract</h2><p>Tuberous Sclerosis Complex (TSC) is an autosomal dominant neurogenetic disorder affecting about 1 in 6,000 people. TSC usually has effects on the central nervous system manifested by a high incidence of seizures, intellectual disability, and autism. TSC is caused by mutations in either TSC1 or TSC2, which encode for proteins that form a complex to inhibit mammalian target of rapamycin complex 1 (mTORC1). mTORC1 is a central regulator of ribosomal biogenesis and translation initiation. Nevertheless, heterozygous loss of Tsc2 leads to diminished protein synthesis both in vitro and in vivo. Specifically, with the in vivo quantitative autoradiographic L-[1-14C]leucine method, we found reduced rates of cerebral protein synthesis (rCPS) in Tsc2+/- mice at 3 months of age, particularly in the parietal cortex, dorsal and ventral hippocampus, and visual cortex. We treated mice with rapamycin to determine if we could reverse this phenotype. We performed both acute and chronic rapamycin studies. For acute studies, we injected 3mg/kg rapamycin i.v., 30 min prior to tracer infusion. For chronic studies, we treated mice from P21 until P90 with rapamycin-enriched chow to achieve a daily dose of approximately 2.2mg/kg. Preliminary results indicate that acute rapamycin treatment of Tsc2+/- mice (n=5) increased rCPS in many brain regions, including thalamus, hippocampus, and parietal cortex compared to vehicle-treated Tsc2+/- mice (n=4). Rapamycin treatment did not significantly alter rCPS in controls. Our preliminary results suggest a complex role of mTORC1 in the regulation of cerebral protein synthesis, a role that is sensitive to rapamycin treatment.</p><p><strong>Scientific Focus Area</strong>: Neuroscience</p><p class="updated"><small>This page was last updated on Friday, March 26, 2021</small></p></article>
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