Formyl peptide receptor as a novel therapeutic target for anxiety-related disorders

Irene Gallo; Lorenza Rattazzi; Giuseppa Piras; Thomas Gobbetti; Elisabetta Panza; Mauro Perretti; Jeffrey W. Dalley; Fulvio D'Acquisto

doi:10.1371/journal.pone.0114626

Formyl peptide receptor as a novel therapeutic target for anxiety-related disorders

Irene Gallo
, Lorenza Rattazzi
, Giuseppa Piras
, Thomas Gobbetti
, Elisabetta Panza
, Mauro Perretti
, Jeffrey W. Dalley
, Fulvio D'Acquisto

Research output: Contribution to journal › Article › peer-review

Abstract

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface.

Original language	English
Pages (from-to)	e114626
Journal	PLoS One
Volume	9
Issue number	12
DOIs	https://doi.org/10.1371/journal.pone.0114626
Publication status	Published - 17 Dec 2014

Keywords

Animals
Anxiety
Corticosterone
Exploratory Behavior
Gene Deletion
Male
Mice
Molecular Targeted Therapy
Nervous System Diseases
Oligopeptides
Receptors, Formyl Peptide
Recognition (Psychology)
Signal Transduction
Journal Article

Access to Document

10.1371/journal.pone.0114626

http://dx.plos.org/10.1371/journal.pone.0114626

Cite this

@article{773c8cfa162f40cebffce6ae933d19cc,

title = "Formyl peptide receptor as a novel therapeutic target for anxiety-related disorders",

abstract = "Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface.",

keywords = "Animals, Anxiety, Corticosterone, Exploratory Behavior, Gene Deletion, Male, Mice, Molecular Targeted Therapy, Nervous System Diseases, Oligopeptides, Receptors, Formyl Peptide, Recognition (Psychology), Signal Transduction, Journal Article",

author = "Irene Gallo and Lorenza Rattazzi and Giuseppa Piras and Thomas Gobbetti and Elisabetta Panza and Mauro Perretti and Dalley, \{Jeffrey W.\} and Fulvio D'Acquisto",

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AU - Gallo, Irene

AU - Rattazzi, Lorenza

AU - Piras, Giuseppa

AU - Gobbetti, Thomas

AU - Panza, Elisabetta

AU - Perretti, Mauro

AU - Dalley, Jeffrey W.

AU - D'Acquisto, Fulvio

PY - 2014/12/17

Y1 - 2014/12/17

N2 - Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface.

AB - Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface.

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KW - Oligopeptides

KW - Receptors, Formyl Peptide

KW - Recognition (Psychology)

KW - Signal Transduction

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