Expression of Fbp2, a Newly Discovered Constituent of Memory Formation Mechanisms, Is Regulated by Astrocyte-Neuron Crosstalk

Int J Mol Sci. 2020 Sep 20;21(18):6903. doi: 10.3390/ijms21186903.


Fbp2 (muscle isozyme of fructose 1,6-bisphosphatase) is a glyconeogenesis-regulating enzyme and a multifunctional protein indispensable for long-term potentiation (LTP) formation in the hippocampus. Here, we present evidence that expression of Fbp2 in murine hippocampal cell cultures is regulated by crosstalk between neurons and astrocytes. Co-culturing of the two cell types results in a decrease in Fbp2 expression in astrocytes, and its simultaneous increase in neurons, as compared to monocultures. These changes are regulated by paracrine signaling using extracellular vesicle (EV)-packed factors released to the culture medium. It is well accepted that astrocyte-neuron metabolic crosstalk plays a crucial role in shaping neuronal function, and recently we have suggested that Fbp2 is a hub linking neuronal signaling with redox and/or energetic state of brain during the formation of memory traces. Thus, our present results emphasize the importance of astrocyte-neuron crosstalk in the regulation of the cells' metabolism and synaptic plasticity, and bring us one step closer to a mechanistic understanding of the role of Fbp2 in these processes.

Keywords: Fbp2; Hif1α; astrocyte–neuron crosstalk; c-Fos; extracellular vesicles.

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / enzymology*
  • Cell Communication*
  • Energy Metabolism
  • Fructose-Bisphosphatase / biosynthesis*
  • Gene Expression Regulation, Enzymologic*
  • Memory*
  • Mice
  • Mice, Inbred BALB C
  • Neuronal Plasticity
  • Neurons / cytology
  • Neurons / enzymology*
  • Signal Transduction*


  • Fructose-Bisphosphatase