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Can FGF21 calm LPS-triggered despair in mice?

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rhFGF21 (0.75–3 mg/kg) improved OFT locomotion and cut FST/TST immobility after LPS 0.83 mg/kg, lowered IL-1β/TNF-α/IL-6 and NF-κB, and lost benefit with FGFR1 inhibitor PD173074.

Source

FGF21 Attenuated LPS-Induced Depressive-Like Behavior <i>via</i> Inhibiting the Inflammatory Pathway

Wang X, Zhu L, Hu J, et al. · Frontiers in pharmacology · 2020

doi.org/10.3389/fphar.2020.00154Read the full paper ↗56 citationscc by

Study at a glance

Design
Animal / in-vitro — Male C57BL/6N mice pretreated with rhFGF21 then LPS 0.83 mg/kg; OFT/FST/TST plus primary microglia; FGFR1 blocker PD173074
N
N=5 · Western blot and related assays reported n=5; three in-vivo groups with rhFGF21 0.75, 1.5, and 3 mg/kg twice daily ×3 days
Population
Male C57BL/6N mice (20–25 g) and primary microglia challenged with LPS
Outcome
Open-field, tail-suspension, and forced-swim despair tests; hippocampal cytokines, Iba1 microglia, NF-κB, and FGFR1 dependence

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

Pretreated male C57BL/6N mice with rhFGF21 twice daily for 3 days, injected LPS 0.83 mg/kg, then ran OFT/FST/TST and hippocampal cytokine/NF-κB/microglia assays (n=5 blots), including PD173074 co-treatment and primary microglia.

What they found

LPS cut FGF21 and caused despair-like behavior; rhFGF21 (especially 1.5–3 mg/kg) restored locomotion, reduced immobility, suppressed IL-1β/TNF-α/IL-6, and blocked microglia/NF-κB. PD173074 reversed protection, implying FGFR1.

The limits

What it doesn't show

LPS sickness is not major depressive disorder; n=5 biochemistry and male-only mice cannot establish a human antidepressant dose.

Key terms

FGF21
Metabolic fibroblast growth factor; recombinant human FGF21 was the drug here.
LPS
Lipopolysaccharide inflammatory challenge (0.83 mg/kg i.p.).
FST/TST
Forced-swim and tail-suspension tests of immobility (despair-like).
FGFR1
FGF receptor 1; PD173074 blockade reversed rhFGF21’s benefit.
NF-κB
Inflammatory transcription pathway suppressed by rhFGF21.
Iba1
Microglial marker used to show activation in hippocampus.

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rhFGF21 was tested against:

Common questions

What LPS dose induced despair-like behavior?

0.83 mg/kg i.p.

What rhFGF21 doses were tested?

0.75, 1.5, and 3 mg/kg twice daily for 3 days.

Which dose went forward?

1.5 mg/kg.

What blocked the benefit?

FGFR1 inhibitor PD173074.

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