{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:20:57Z","timestamp":1771719657512,"version":"3.50.1"},"reference-count":47,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We tested the hypothesis that exposure of glut3+\/\u2212 mice to a ketogenic diet ameliorates autism-like features, which include aberrant behavior and electrographic seizures. We first investigated the life course sex-specific changes in basal plasma\u2013cerebrospinal fluid (CSF)\u2013brain metabolic profile, brain glucose transport\/uptake, glucose and monocarboxylate transporter proteins, and adenosine triphosphate (ATP) in the presence or absence of systemic insulin administration. Glut3+\/\u2212 male but not female mice (5 months of age) displayed reduced CSF glucose\/lactate concentrations with no change in brain Glut1, Mct2, glucose uptake or ATP. Exogenous insulin-induced hypoglycemia increased brain glucose uptake in glut3+\/\u2212 males alone. Higher plasma-CSF ketones (\u03b2-hydroxybutyrate) and lower brain Glut3 in females vs males proved protective in the former while enhancing vulnerability in the latter. As a consequence, increased synaptic proteins (neuroligin4 and SAPAP1) with spontaneous excitatory postsynaptic activity subsequently reduced hippocampal glucose content and increased brain amyloid \u03b21-40 deposition in an age-dependent manner in glut3+\/\u2212 males but not females (4 to 24 months of age). We then explored the protective effect of a ketogenic diet on ultrasonic vocalization, sociability, spatial learning and memory, and electroencephalogram seizures in male mice (7 days to 6 to 8 months of age) alone. A ketogenic diet partially restored sociability without affecting perturbed vocalization, spatial learning and memory, and reduced seizure events. We conclude that (1) sex-specific and age-dependent perturbations underlie the phenotype of glut3+\/\u2212 mice, and (2) a ketogenic diet ameliorates seizures caused by increased cortical excitation and improves sociability, but fails to rescue vocalization and cognitive deficits in glut3+\/\u2212 male mice.<\/jats:p>","DOI":"10.1210\/en.2016-1816","type":"journal-article","created":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T02:52:56Z","timestamp":1491447176000},"page":"936-949","source":"Crossref","is-referenced-by-count":26,"title":["Sex-Specific Life Course Changes in the Neuro-Metabolic Phenotype of Glut3 Null Heterozygous Mice: Ketogenic Diet Ameliorates Electroencephalographic Seizures and Improves Sociability"],"prefix":"10.1210","volume":"158","author":[{"given":"Yun","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology & Developmental Biology, Neonatal Research Center at the UCLA Children\u2019s Discovery and 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