Neuronal glucose transporter isoform 3 deficient mice demonstrate features of autism spectrum disorders.
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 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.
Zhao
Y
Y
Division of Neonatology, Neonatal Research Center, David Geffen School of Medicine UCLA, Los Angeles, CA 90095, USA.
Fung
C
C
Shin
D
D
Shin
B-C
BC
Thamotharan
S
S
Sankar
R
R
Ehninger
D
D
Silva
A
A
Devaskar
S U
SU
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D004195:Disease Models, Animal; D051272:Glucose Transporter Type 1 / Q000235:genetics* / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012640:Seizures / Q000235:genetics; D014828:Vocalization, Animal / Q000502:physiology
D015816:Cell Adhesion Molecules, Neuronal; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D008565:Membrane Proteins; D027501:Monocarboxylic Acid Transporters; D009419:Nerve Tissue Proteins; C098004:neuroligin 3; D019344:Lactic Acid; D003847:Deoxyglucose