TY - JOUR
T1 - Recurrent major depressive disorder
T2 - Imbalance of neurokinin (NK)-1 and NK-2 receptor expression in monocytes
AU - Bardelli, Claudio
AU - Amoruso, Angela
AU - Manzetti, Elena
AU - Fresu, Luigia Grazia
AU - Valsesia, Roberta
AU - Zeppegno, Patrizia
AU - Brunelleschi, Sandra
N1 - Funding Information:
This work was partially granted by Regione Piemonte, Ricerca Sanitaria Finalizzata . We thank Dr. Daniela Renzi, University of Florence (Italy), for the kind gift of the NK-2R antibody. We would like to thank Dr. G. Castignoli and Dr. P. Mainini for help in recruiting outpatients in the Psychiatric Service of Borgomanero (Novara) and Dr. E. Quadro for help in recruiting outpatients in the Psychiatric Service of Arona (Novara). Angela Amoruso's work was supported by a post doc fellowship from Cariplo Foundation, NutriAl Network 2010.
PY - 2013/2
Y1 - 2013/2
N2 - Increasing evidence suggests that tachykinins are involved in the control of different pathological conditions, including psychiatric disorders. In this study we evaluated the expression of NK1 and NK2 receptors (NK-1R and NK-2R), as well as the effects of substance P (SP) and neurokinin A (NKA), in monocytes isolated from 15 healthy subjects and 15 patients with recurrent major depressive disorder (RMDD), under stable antidepressant therapy. NK-1R expression in monocytes from RMDD patients was significantly decreased as compared to healthy subjects, whereas NK-2R expression was markedly increased. Both NK-1R and NK-2R expression correlated with HAM-D, but not HAM-A, score. SP, NKA and selective NK-1R and NK-2R agonists stimulated TNF-α release in monocytes of both groups, with a significant higher effect observed in RMDD. Moreover they induced NF-κB activation, which was reversed by selective NK-1R and NK-2R antagonists, so demonstrating that it was receptor-mediated. The occurrence of a profound alteration in NK receptor expression in RMDD is a novel finding that suggests NK-1R and NK-2R pathways as possible relevant players in major depressive disorder, so improving our understanding of the complex pathogenesis of the disease.
AB - Increasing evidence suggests that tachykinins are involved in the control of different pathological conditions, including psychiatric disorders. In this study we evaluated the expression of NK1 and NK2 receptors (NK-1R and NK-2R), as well as the effects of substance P (SP) and neurokinin A (NKA), in monocytes isolated from 15 healthy subjects and 15 patients with recurrent major depressive disorder (RMDD), under stable antidepressant therapy. NK-1R expression in monocytes from RMDD patients was significantly decreased as compared to healthy subjects, whereas NK-2R expression was markedly increased. Both NK-1R and NK-2R expression correlated with HAM-D, but not HAM-A, score. SP, NKA and selective NK-1R and NK-2R agonists stimulated TNF-α release in monocytes of both groups, with a significant higher effect observed in RMDD. Moreover they induced NF-κB activation, which was reversed by selective NK-1R and NK-2R antagonists, so demonstrating that it was receptor-mediated. The occurrence of a profound alteration in NK receptor expression in RMDD is a novel finding that suggests NK-1R and NK-2R pathways as possible relevant players in major depressive disorder, so improving our understanding of the complex pathogenesis of the disease.
KW - Monocytes
KW - NF-κB
KW - NK-1 and NK-2 receptors
KW - Neurokinin A
KW - Recurrent major depressive disorder
KW - Substance P
UR - https://www.scopus.com/pages/publications/84872326236
U2 - 10.1016/j.phrs.2012.10.022
DO - 10.1016/j.phrs.2012.10.022
M3 - Article
SN - 1043-6618
VL - 68
SP - 24
EP - 30
JO - Pharmacological Research
JF - Pharmacological Research
IS - 1
ER -