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Updated: Jul 14, 2026
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Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
Published on: May 12, 2015
FGF21 Exhibits Neuroprotective Effects by Promoting 5-HT1AR-FGFR1 Heteroreceptor Complexes and Triggering
Qian Yan1, Xiao-Jun Li1, Qi-Qi Wang1
1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
Molecular Neurobiology
|January 9, 2025
Summary
Fibroblast growth factor 21 (FGF21) protects the brain by forming FGFR1-5-HT1A receptor complexes and activating the ERK pathway. This mechanism alleviates neurological damage and promotes neuronal resilience in various conditions.
Area of Science:
- Neuroscience
- Molecular Biology
- Endocrinology
Background:
- Promoting neural plasticity and resilience is crucial for treating neurological disorders.
- Fibroblast growth factor 21 (FGF21) exhibits neuroprotective properties, but its mechanisms are unclear.
- FGF21 is a known regulator of glucose and energy metabolism.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying the neuroprotective effects of FGF21.
- To investigate FGF21's role in promoting 5-HT1A receptor-FGFR1 heteroreceptor formation and MEK1/2-ERK1/2 signaling.
- To assess FGF21's efficacy in normal and neurologically impaired conditions.
Main Methods:
- In vitro cell culture experiments to assess FGF21's effect on glutamate-induced cytotoxicity.
- In vivo studies using wild-type and FGF21 knockout mice.
- Analysis of hippocampal tissue from mice subjected to neurological injury or stress.
Main Results:
- FGF21 demonstrated protective effects against glutamate toxicity and promoted cell growth in vitro.
- Exogenous FGF21 induced FGFR1-5-HT1A heteromer formation and activated the MEK1/2-ERK1/2 pathway in mouse hippocampus.
- FGF21 treatment phosphorylated FGFR1 and increased synaptophysin expression in injured or stressed mice.
Conclusions:
- FGF21 alleviates neurological impairment by facilitating FGFR1-5-HT1A heteromer formation and activating the ERK1/2 signaling pathway.
- Regulation of FGFR1-5-HT1A heteromers and the MEK1/2/ERK1/2 pathway is key to FGF21's neuroprotective effects.
- FGF21 holds potential for treating neurodegenerative conditions by enhancing neuronal resilience.
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