Biosynthesis of Astrocytic Trehalose Regulates Neuronal Arborization in Hippocampal Neurons

Trehalose
is a nonreducing disaccharide that has recently attracted
much attention because of its ability to inhibit protein aggregation,
induce autophagy, and protect against dissections and strokes. In
vertebrates, the biosynthesis of trehalose was long considered absent
due to the lack of annotated genes involved in this process. In contrast,
trehalase (TreH), which is an enzyme required for the cleavage of
trehalose, is known to be conserved and expressed. Here, we show that
trehalose is present as an endogenous metabolite in the rodent hippocampus.
We found that primary astrocytes were able to synthesize trehalose
and release it into the extracellular space. Notably, the TreH enzyme
was observed only in the soma of neurons, which are the exclusive
users of this substrate. A statistical analysis of the metabolome
during different stages of maturation indicated that this metabolite
is implicated in neuronal maturation. A morphological analysis of
primary neurons confirmed that trehalose is required for neuronal
arborization.