High-fructose corn syrup consumption in adolescent rats causes bipolar-like behavioural phenotype with hyperexcitability in hippocampal CA3-CA1 synapses

Autor:	Sadik Taskin Tas, Erva Bayraktar, Yildirim Sara, Baris Alten, Canan Kurşungöz, Metin Yesiltepe, Ayse Yesim Gocmen, Ana Martínez
Rok vydání:	2018
Předmět:	0301 basic medicine Pharmacology medicine.medical_specialty food.ingredient Lithium (medication) High-fructose corn syrup Hippocampus AMPA receptor Hippocampal formation Biology Corn syrup 03 medical and health sciences Electrophysiology 030104 developmental biology 0302 clinical medicine food Endocrinology GSK-3 Internal medicine medicine 030217 neurology & neurosurgery medicine.drug
Zdroj:	British Journal of Pharmacology. 175:4450-4463
ISSN:	0007-1188
DOI:	10.1111/bph.14500
Popis:	BACKGROUND AND PURPOSE Children and adolescents are the top consumers of high-fructose corn syrup (HFCS) sweetened beverages. Even though the cardiometabolic consequences of HFCS consumption in adolescents are well known, the neuropsychiatric consequences have yet to be determined. EXPERIMENTAL APPROACH Adolescent rats were fed for a month with 11% weight/volume carbohydrate containing HFCS solution, which is similar to the sugar-sweetened beverages of human consumption. The metabolic, behavioural and electrophysiological characteristics of HFCS-fed rats were determined. Furthermore, the effects of TDZD-8, a highly specific GSK-3B inhibitor, on the HFCS-induced alterations were further explored. KEY RESULTS HFCS-fed adolescent rats displayed bipolar-like behavioural phenotype with hyperexcitability in hippocampal CA3-CA1 synapses. This hyperexcitability was associated with increased presynaptic release probability and increased readily available pool of AMPA receptors to be incorporated into the postsynaptic membrane, due to decreased expression of the neuron-specific α3-subunit of Na+ /K+ -ATPase and an increased ser845 -phosphorylation of GluA1 subunits (AMPA receptor subunit) respectively. TDZD-8 treatment was found to restore behavioural and electrophysiological disturbances associated with HFCS consumption by inhibition of GSK-3B, the most probable mechanism of action of lithium for its mood-stabilizing effects. CONCLUSION AND IMPLICATIONS This study shows that HFCS consumption in adolescent rats led to a bipolar-like behavioural phenotype with neuronal hyperexcitability, which is known to be one of the earliest endophenotypic manifestations of bipolar disorder. Inhibition of GSK-3B with TDZD-8 attenuated hyperexcitability and restored HFCS-induced behavioural alterations.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::c86430ae9eb72a28955b9c603f68e85b https://doi.org/10.1111/bph.14500 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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