Stimulating transformation of glucose molecules into lipids in neurons is an essential factor for the development of neural networks, according to a study published in The EMBO Journal –publication of the European Molecular Biology Laboratory- and led by Professor Francesc X. Soriano, of the Faculty of Biology and the Institute of Neurosciences of the UB (UBNeuro). The lecturers Manuel Reina (Faculty of Biology of the UB) and Ofèlia M. Martínez (Faculty of Biology of the UB and Institute of Biomedicine of the UB, IBUB) and other experts have participated in the study as well.
The neuron is a cell that transmits the nervous stimulus which is built by some –cell body- and a series of branches (dendrites and axons). The development of axons and andrites favours the establishment of neural networks, a process that determines each person’s cognitive skills. Actually, the alteration of dendritic development is the main anatomic feature in medical profiles of intellectual disability.
More lipid synthesis to expand the neural membrane
According to Professor Francesc X. Soriano, from the Department of Cell Biology, Physiology and Immunology, “communication between neurons is one of the main factors that control the growth of axons and dendrites. For this growth to appear, a series of changes in the cytoskeleton and an increase of lipid components to expand the surface of the neural membrane is necessary”.
“Although the changes that occur at the cytoskeleton level are known –continues Soriano- so far there was not enough information on which metabolic changes occurred in the neuron to synthetize the necessary lipids and expand the cell membrane”.
Discovering that the increase of glucose’s metabolism is essential for the growth of axons and dendrites is the most outstanding scientific contribution of the researcher Marc Segarra (UB-UBNeuro) –first author of the study- in collaboration with the experts of the Celltec-UB research group and Universidad Autónoma de Madrid. “This process is essential because a part of this glucose goes to the synthesis of lipids that allow an expansion of the surface of the neural membrane” notes Segarra, also member of Celltec-UB.
Strategies to boost glucose’s metabolism in neurons
The scientific team has determined the molecular mechanism that stimulates the recruitment and metabolism of glucose in the synaptic activity between neurons. According to the new study, this is regulated by the genic expression of the glucose transporter Glut3 –through the protein CREB- and rate-limiting genes of glucose’s metabolism through the participation of the hypoxia1-induced factor (HIF-1α).
According to the authors, “pharmacological and genetic manipulation of glucose’s metabolism in neurons –both in vitro and in vivo- affects neural morphology. Therefore, the study in The EMBO Journal could open new therapeutic ways for the treatment of disorders that are related to brain development”.
The new study received funding from the Ministry of Economy, Industry and Competitiveness (MINECO), the European Regional Development Fund (ERDF), Ramón Areces Foundation and Tatiana Pérez de Guzman el Bueno Foundation.
Segarra-Mondejar, M.; Casellas-Díaz, S.; Ramiro-Pareta, M.; Müller-Sánchez, C.; Martorell-Riera, A.; Hermelo, I.; Reina, M.; Aragonés, J.; Martínez-Estrada, O. M.; Soriano, F. X. «Synaptic activity-induced glycolysis facilitates membrane lipid provision and neurite outgrowth». The EMBO Journal, 2018 April 3. doi: 10.15252/embj.201797368
Universitat de Barcelona