Neural Deletion of Glucose Transporter Isoform 3 Creates Distinct Postnatal and Adult Neurobehavioral Phenotypes

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Bo-Chul ShinSherin U Devaskar

Abstract

We created a neural-specific conditional murine glut3 (Slc2A3) deletion (glut3flox/flox/nestin-Cre+) to examine the effect of a lack of Glut3 on neurodevelopment. Compared with age-matched glut3flox/flox = WT and heterozygotes (glut3flox/+/nestin-Cre+), we found that a >90% reduction in male and female brain Glut3 occurred by postnatal day 15 (PN15) in glut3flox/flox/nestin-Cre+ This genetic manipulation caused a diminution in brain weight and cortical thickness at PN15, a reduced number of dendritic spines, and fewer ultrasonic vocalizations. Patch-clamp recordings of cortical pyramidal neurons revealed increased frequency of bicuculline-induced paroxysmal discharges as well as reduced latency, attesting to a functional synaptic and cortical hyperexcitability. Concomitant stunting with lower glucose concentrations despite increased milk intake shortened the lifespan, failing rescue by a ketogenic diet. This led to creating glut3flox/flox/CaMK2α-Cre+ mice lacking Glut3 in the adult male limbic system. These mice had normal lifespan, displayed reduced IPSCs in cortical pyramidal neurons, less anxiety/fear, and lowered spatial memory and motor abilities but heightened exploratory and social responses. These distinct postnatal and...Continue Reading

Citations

Jun 28, 2020·Pflügers Archiv : European journal of physiology·Alexandra Chadt, Hadi Al-Hasani
Aug 20, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jiayi ZhuBo Hu
May 7, 2020·Journal of Cellular Physiology·Georg C ZieglerKlaus-Peter Lesch
Aug 24, 2021·Metabolism: Clinical and Experimental·Wuxue PengLifen Chen
Jan 1, 2022·Cellular and Molecular Life Sciences : CMLS·Yen T K NguyenLong N Nguyen

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