Neuronal glucose transporter (GLUT) isoform 3 deficiency in null heterozygous mice led to abnormal spatial learning and working memory but normal acquisition and retrieval during contextual conditioning, abnormal cognitive flexibility with intact gross motor ability, electroencephalographic seizures, perturbed social behavior with reduced vocalization and stereotypies at low frequency. This phenotypic expression is unique as it combines the neurobehavioral with the epileptiform characteristics of autism spectrum disorders. This clinical presentation occurred despite metabolic adaptations consisting of an increase in microvascular/glial GLUT1, neuronal GLUT8 and monocarboxylate transporter (MCT) isoform 2 concentrations, with minimal to no change in brain glucose uptake but an increase in lactate uptake. Neuron-specific glucose deficiency has a negative impact on neurodevelopment interfering with functional competence. This is the first description of GLUT3 deficiency that forms a possible novel genetic mechanism for pervasive developmental disorders, such as the neuropsychiatric autism spectrum disorders, requiring further investigation in humans.

We examined the effects of 45 min hypoxia (FiO2 0.08, Hx) versus normoxia (FiO2 0.21, Nx) on the ipsilateral (Ipsi) and contralateral (Ctrl) sides of the brain in neuronal glucose transporter isoform 3 (Glut3) heterozygous null mice (glut3+/−) and their wild type littermates (WT), undergoing unilateral carotid artery ligation. Glut3+/− mice, under Nx, demonstrated a compensatory increase in blood-brain barrier/glial Glut1 protein concentration, a concomitant increase in neuronal nitric oxide synthase (nNOS) enzyme activity and Bax protein, with a decrease in pro-caspase 3 protein (p<0.05 each). After Hx, re-oxygenation in FiO2 of 0.21 led to no comparable adaptive up-regulation of the ipsilateral brain Glut3 or Glut1 protein at 4 hr and Glut1 at 24hrs in glut3+/− versus WT. These brain Glut changes in glut3+/− but not WT mice were associated with an increase in pro-apoptotic Bax protein and caspase-3 enzyme activity (p<0.01 each) and a decline in the anti-apoptotic Bcl-2 and procaspase-3 proteins (p<0.05 each). Glut3+/− mice after Hx demonstrated TUNEL positive neurons with nuclear pyknosis in most ipsilateral (hypoxic-ischemia) brain regions. A sub-set (~55%) of glut3+/− mice developed spontaneous seizures after hypoxic-ischemia confirmed by electroencephalography while the WT mice remained seizure-free. Pentylenetetrazole testing demonstrated an increased occurrence of longer lasting clinical seizures at a lower threshold in glut3+/− versus WT mice, with no detectable differences in monamine neurotransmitters. We conclude that hypoxic-ischemic brain injury in glut3+/− mice exacerbates cellular apoptosis, necrosis and precipitates spontaneous seizures.

High concentrations of ultrafine particles (UFPs) have been previously reported during school art activities. This is possibly due to secondary organic aerosols (SOAs) formed from reactions between ozone and volatile organic compounds emitted from art products. Four brands of markers, three scented and one unscented, were tested inside a stainless steel chamber at eight different ozone concentrations between 0 and 300 ppb. Out of the 32 tested markers, only the lemon- and orange-scented markers from one brand reacted with ozone to form UFPs. Limonene, pinene, and several other terpenes were identified as ingredients of ink in SOA-forming markers. Coloring with one lemon-scented marker for 1 min without ozone generated on average approximately 26 ± 4 ppb of limonene inside the chamber. At 150 ppb ozone, using one lemon marker for 1 min formed on average 7.7 × 10(10) particles. The particle size distribution indicated an initial mode of 15 nm which grew to 40 nm. At 50 ppb ozone and below, no significant SOA formation occurred. The number of particles formed is moderately correlated with the mass of ink used (R(2)  = 0.68). Based on these data, scented markers are not likely a strong source of SOA under normal indoor ozone levels.

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