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Updated: Oct 2, 2025
Strategies for Assessing Autistic-Like Behaviors in Mice
Published on: September 20, 2024
Behavioral, Anti-Inflammatory, and Neuroprotective Effects of a Novel FPR2 Agonist in Two Mouse Models of Autism
Claudia Cristiano1, Floriana Volpicelli1, Marianna Crispino2
1Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy.
Insights
A new compound, MR-39, targeting the formyl peptide receptor 2 (FPR2), improved social behaviors and neuronal plasticity in autism spectrum disorder (ASD) animal models. This suggests FPR2 as a potential therapeutic target for ASD.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Autism spectrum disorders (ASD) are neurodevelopmental conditions marked by social deficits and altered inflammation.
- Children with ASD exhibit reduced levels of lipoxin A4 (LXA4), an inflammation resolution mediator and formyl peptide receptor 2 (FPR2) ligand.
Purpose of the Study:
- To investigate the role of FPR2 in ASD using a novel FPR2-activating compound, MR-39.
- To evaluate the therapeutic potential of MR-39 in established animal models of ASD.
Main Methods:
- MR-39 was administered to BTBR mice and valproic acid (VPA)-exposed mice, validated ASD models.
- Effects on hippocampal inflammation, neuronal plasticity, and social behavior were assessed.
- Neurite elongation was evaluated in primary hippocampal neuron cultures.
Main Results:
- MR-39 treatment reduced pro-inflammatory markers and normalized LXA4 levels in the hippocampus.
- The compound modulated FPR2 expression in ASD animal models.
- MR-39 significantly improved social behaviors and stimulated neurite elongation in hippocampal neurons.
Conclusions:
- These findings highlight FPR2 as a promising therapeutic target for autism spectrum disorders.
- MR-39 demonstrates potential for developing novel treatments for ASD by modulating inflammation and promoting neuronal plasticity.
Abstract:
Autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental conditions characterized by social deficits, repetitive stereotyped behaviors, and altered inflammatory responses. Accordingly, children with ASD show decreased plasma levels of lipoxin A4 (LXA4), a mediator involved in the resolution of inflammation, which is the endogenous ligand of the formyl peptide receptor 2 (FPR2). To investigate the role of FPR2 in ASDs, we have used a new ureidopropanamide derivative able to activate the receptor, named MR-39. The effects of MR-39 (10 mg/kg, for 8 days) on hippocampal pro-inflammatory profile, neuronal plasticity, and social behavior were evaluated in two validated animal models of ASD: BTBR mouse strain and mice prenatally exposed to valproic acid (VPA). Primary cultures of hippocampal neurons from BTBR mice were also used to evaluate the effect of MR-39 on neurite elongation. Our results show that MR-39 treatment reduced several inflammatory markers, restored the low expression of LXA4, and modulated FPR2 expression in hippocampal tissues of both ASD animal models. These findings were accompanied by a significant positive effect of MR-39 on social behavioral tests of ASD mice. Finally, MR-39 stimulates neurite elongation in isolated hippocampal neurons of BTBR mice. In conclusion, these data indicate FPR2 as a potential target for an innovative therapeutical approach for the cure of ASD.
