# Exogenous L-fucose attenuates depression induced by chronic unpredictable stress: Implicating core fucosylation has an antidepressant potential

## TL;DR

L-fucose reduces depressive behaviors and neuroinflammation in mice, suggesting core fucosylation may have antidepressant potential.

## Contribution

This study reveals that exogenous L-fucose has antidepressant effects by modulating neuroinflammation and synaptic defects.

## Key findings

- L-fucose reduced depressive-like behaviors and pro-inflammatory cytokines in mice with CUS-induced depression.
- L-fucose treatment increased dendritic spine density and PSD-95 expression suppressed by CUS.
- Antidepressant effects of L-fucose were observed in both Fut8+/− and Fut8+/+ mice.

## Abstract

Core fucosylation is one of the most essential modifications of the N-glycans, catalyzed by α1,6-fucosyltransferase (Fut8), which transfers fucose from guanosine 5′-diphosphate (GDP)-fucose to the innermost N-acetylglucosamine residue of N-glycans in an α1-6 linkage. Our previous studies demonstrated that lipopolysaccharide (LPS) can induce a more robust neuroinflammatory response in Fut8 homozygous knockout (KO) (Fut8−/−) and heterozygous KO (Fut8+/−) mice contrasted to the wild-type (Fut8+/+) mice. Exogenous administration of L-fucose suppressed LPS-induced neuroinflammation. Numerous studies indicate that neuroinflammation plays a vital role in the development of depression. Here, we investigated whether core fucosylation regulates depression induced by chronic unpredictable stress (CUS), a well-established model for depression. Our results showed that Fut8+/− mice exhibited depressive-like behaviors and increased neuroinflammation earlier than Fut8+/+ mice. Administration of L-fucose significantly reduced CUS-induced depressive-like behaviors and pro-inflammatory cytokine levels in Fut8+/− mice. The L-fucose treatment produced antidepressant effects by attenuating the complex formation between gp130 and the interleukin-6 (IL-6) receptor and the JAK2/STAT3 signaling pathway. Notably, L-fucose treatment increased dendritic spine density and postsynaptic density protein 95 (PSD-95) expression, which were suppressed in CUS-induced depression. Furthermore, the effects of L-fucose on the CUS-induced depression were also observed in Fut8+/+ mice. Our results clearly demonstrate that L-fucose ameliorates neuroinflammation and synaptic defects in CUS-induced depression, implicating that core fucosylation has significant anti-neuroinflammatory activity and an antidepressant potential.