Glucose Overload Inhibits Glutamatergic Synaptic Transmission: A Novel Role for CREB-Mediated Regulation of Synaptotagmins 2 and 4

Cristian Ripoli, Salvatore Fusco, Claudio Grassi, Matteo Spinelli, Francesca Natale

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

Abstract

Glucose metabolism derangement is critically involved in the age-related memory loss but the underlying molecular mechanisms are still poorly understood. In a mouse model of type 1 diabetes we found memory impairment associated with inhibition of the transcription factor CREB and alteration of pre- and post-synaptic protein expression in the hippocampus. Accordingly, glucose excess negatively affected activity-dependent CREB phosphorylation and CREB-mediated mRNA expression of synaptic proteins in hippocampal primary neurons. Specifically, glucose excess inhibited the activity-dependent recruitment of CREB on the regulatory sequences of synaptotagmin (SYT) 2 and 4 promoters and the expression of SYT4 protein. As a result, high glucose affected both the frequency of miniature excitatory postsynaptic currents and NMDA receptor-mediated currents in autaptic hippocampal neuronal cultures. Collectively, our findings highlight novel mechanisms underlying hyperglycaemia-related memory loss, including CREB-dependent downregulation of synaptotagmin expression
Lingua originaleEnglish
pagine (da-a)N/A-N/A
Numero di pagine13
RivistaFrontiers in Cell and Developmental Biology
Volume2020
DOI
Stato di pubblicazionePubblicato - 2020

Keywords

  • hippocampus
  • hyperglycaemia
  • memory loss
  • metabolism
  • synaptic proteins
  • synaptic vesicle release
  • type 1 diabetes

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