Browsing by Author "Bayraktar, E."

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Open Access
High-fructose corn syrup consumption in adolescent rats causes bipolar-like behavioural phenotype with hyperexcitability in hippocampal CA3-CA1 synapses
(John Wiley and Sons, 2018) Alten, B.; Yesiltepe, M.; Bayraktar, E.; Tas, S. T.; Gocmen, A. Y.; Kursungoz, C.; Martinez, A.; Sara, Y.
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.
Open Access
Revisiting the complex architecture of ALS in Turkey: expanding genotypes, shared phenotypes, molecular networks, and a public variant database
(John Wiley and Sons, 2020) Tunca, C.; Şeker, T.; Akçimen, F.; Coşkun, C.; Bayraktar, E.; Palvadeau, R.; Zor, S.; Koçoğlu, C.; Kartal, E.; Şen, N. E.; Hamzeiy, H.; Özoğuz-Erimiş, A.; Norman, Utku; Karakahya, Oğuzhan; Olgun, Gülden; Akgün, T.; Durmuş, H.; Şahin, E.; Çakar, A.; Başar-Gürsoy, E.; Babacan-Yıldız, G.; İşak, B.; Uluç, K.; Hanağası, H.; Bilgiç, B.; Turgut, N.; Aysal, F.; Ertaş, M.; Boz, C.; Kotan, D.; İdrisoğlu, H.; Soysal, A.; Uzun-Adatepe, N.; Akalın, M. A.; Koç, F.; Tan, E.; Oflazer, P.; Deymeer, F.; Taştan, Ö.; Çiçek, A. Ercüment; Kavak, E.; Parman, Y.; Başak, A. N.
The last decade has proven that amyotrophic lateral sclerosis (ALS) is clinically and genetically heterogeneous, and that the genetic component in sporadic cases might be stronger than expected. This study investigates 1,200 patients to revisit ALS in the ethnically heterogeneous yet inbred Turkish population. Familial ALS (fALS) accounts for 20% of our cases. The rates of consanguinity are 30% in fALS and 23% in sporadic ALS (sALS). Major ALS genes explained the disease cause in only 35% of fALS, as compared with ~70% in Europe and North America. Whole exome sequencing resulted in a discovery rate of 42% (53/127). Whole genome analyses in 623 sALS cases and 142 population controls, sequenced within Project MinE, revealed well‐established fALS gene variants, solidifying the concept of incomplete penetrance in ALS. Genome‐wide association studies (GWAS) with whole genome sequencing data did not indicate a new risk locus. Coupling GWAS with a coexpression network of disease‐associated candidates, points to a significant enrichment for cell cycle‐ and division‐related genes. Within this network, literature text‐mining highlights DECR1, ATL1, HDAC2, GEMIN4, and HNRNPA3 as important genes. Finally, information on ALS‐related gene variants in the Turkish cohort sequenced within Project MinE was compiled in the GeNDAL variant browser (www.gendal.org).