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

TY - JOUR

T1 - Formyl peptide receptor as a novel therapeutic target for anxiety-related disorders

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.

KW - Animals

KW - Anxiety

KW - Corticosterone

KW - Exploratory Behavior

KW - Gene Deletion

KW - Male

KW - Mice

KW - Molecular Targeted Therapy

KW - Nervous System Diseases

KW - Oligopeptides

KW - Receptors, Formyl Peptide

KW - Recognition (Psychology)

KW - Signal Transduction

KW - Journal Article

U2 - 10.1371/journal.pone.0114626

DO - 10.1371/journal.pone.0114626

M3 - Article

C2 - 25517119

SN - 1932-6203

VL - 9

SP - e114626

JO - PLoS One

JF - PLoS One

IS - 12

ER -