{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:19:54Z","timestamp":1788931194903,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T00:00:00Z","timestamp":1522627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000297","name":"FRAXA Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000297","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["ZIAMH00889"],"award-info":[{"award-number":["ZIAMH00889"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000073","name":"Autism Speaks","doi-asserted-by":"publisher","award":["8679"],"award-info":[{"award-number":["8679"]}],"id":[{"id":"10.13039\/100000073","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Tuberous sclerosis complex (<jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>) is an autosomal dominant neurogenetic disorder affecting about 1 in 6000 people and is caused by mutations in either <jats:italic><jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>1<\/jats:italic> or <jats:italic><jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>2<\/jats:italic>. This disorder is characterized by increased activity of mammalian target of rapamycin complex 1 (<jats:styled-content style=\"fixed-case\">mTORC<\/jats:styled-content>1), which is involved in regulating ribosomal biogenesis and translation initiation. We measured the effects of <jats:italic>Tsc2<\/jats:italic> haploinsufficiency (<jats:italic>Tsc2<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup>) in 3\u2010month\u2010old male mice on regional rates of cerebral protein synthesis (<jats:styled-content style=\"fixed-case\">rCPS<\/jats:styled-content>) by means of the <jats:italic>in\u00a0vivo<\/jats:italic> L\u2010[1\u2010<jats:sup>14<\/jats:sup>C]leucine method. This quantitative autoradiographic method includes an estimate of the integrated specific activity of the tracer amino acid in brain tissue. The estimate accounts for recycling of unlabeled amino acids from tissue protein breakdown by means of a factor (\u03bb) that was determined in control and <jats:italic>Tsc2<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> mice. The value of \u03bb was higher in <jats:italic>Tsc2<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> mice, indicating that a greater fraction of leucine in the tissue precursor pool for protein synthesis is derived from the plasma compared to controls, consistent with reduced rates of protein degradation. We determined <jats:styled-content style=\"fixed-case\">rCPS<\/jats:styled-content> in freely moving, awake male <jats:italic>Tsc2<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> and control mice, and we used the determined values of \u03bb in the calculation of <jats:styled-content style=\"fixed-case\">rCPS<\/jats:styled-content>. Unexpectedly, we found that <jats:styled-content style=\"fixed-case\">rCPS<\/jats:styled-content> were significantly decreased in 16 of the 17 brain regions analyzed in <jats:italic>Tsc2<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> mice compared to controls. Our results indicate a complex role of <jats:styled-content style=\"fixed-case\">mTORC<\/jats:styled-content>1 in the regulation of cerebral protein synthesis that has not been previously recognized.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14311-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14311","type":"journal-article","created":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T16:20:46Z","timestamp":1516810846000},"page":"417-425","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Decreased rates of cerebral protein synthesis measured <i>in\u00a0vivo<\/i> in a mouse model of Tuberous Sclerosis Complex: unexpected consequences of reduced tuberin"],"prefix":"10.1111","volume":"145","author":[{"given":"Rachel Michelle","family":"Sar\u00e9","sequence":"first","affiliation":[{"name":"Section\u00a0on Neuroadaptation and Protein Metabolism National Institute of Mental Health National Institutes of Health Department of Health and Human Services Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjian","family":"Huang","sequence":"additional","affiliation":[{"name":"Section\u00a0on Neuroadaptation and Protein Metabolism National Institute of Mental Health National Institutes of Health Department of Health and Human Services Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Burlin","sequence":"additional","affiliation":[{"name":"Section\u00a0on Neuroadaptation and Protein Metabolism National Institute of Mental Health National Institutes of Health Department of Health and Human Services Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Loutaev","sequence":"additional","affiliation":[{"name":"Section\u00a0on Neuroadaptation and Protein Metabolism National Institute of Mental Health National Institutes of Health Department of Health and Human Services Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2722-0180","authenticated-orcid":false,"given":"Carolyn Beebe","family":"Smith","sequence":"additional","affiliation":[{"name":"Section\u00a0on Neuroadaptation and Protein Metabolism National Institute of Mental Health National Institutes of Health Department of Health and Human Services Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10658"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0046-15.2015"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"5926","DOI":"10.1523\/JNEUROSCI.0778-09.2009","article-title":"Tuberous sclerosis complex activity is required to control neuronal stress responses in an mTOR\u2010dependent manner","volume":"29","author":"Nardo A.","year":"2009","journal-title":"J. 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