Regulation of feeding and anxiety by alpha-MSH reactive autoantibodies.
alpha-Melanocyte-stimulating hormone (alpha-MSH) is a stress-related neuropeptide involved in the regulation of motivated behavior, appetite and emotion including stimulation of satiety and anxiety. Although autoantibodies (autoAbs) reactive with alpha-MSH have been identified in human subjects and in rats, it remained unknown if these autoAbs are involved in the regulation of feeding and anxiety and if their production is related to stress. Here we show that repeated exposure of rats to anxiolytic mild stress by handling increases the levels and affinity of alpha-MSH reactive IgG autoAbs and that these changes are associated with adaptive feeding and anxiety responses during exposure of rats to a strong stress by food restriction. Importantly, an increase in affinity of alpha-MSH reactive autoAbs was associated with changes of their functional roles from stimulation to inhibition of alpha-MSH-mediated behavioural responses, suggesting that these autoAbs can be a carrier or a neutralizing molecule of alpha-MSH peptide, respectively. Using a model of passive transfer into the brain, we show that alpha-MSH autoAbs affinity purified from blood of rats exposed to repeated mild stress, but not from control rats, are able to increase acutely food intake, suppress anxiety and modify gene expression of hypothalamic neuropeptides in naïve rats. These data provide the first evidence that autoAbs reactive with alpha-MSH are involved in the physiological regulation of feeding and mood, supporting a further role of the immune system in the control of motivated behavior and adaptation to stress.
Digestive System & Nutrition Laboratory (ADEN EA4311), Institute of Biomedical Research, Rouen University & Hospital, IFR23, 76183 Rouen, France.
Maria Hamze
MH
Sinno
Jean Claude
JC
Do Rego
Moïse
M
Coëffier
Christine
C
Bole-Feysot
Philippe
P
Ducrotté
Danièle
D
Gilbert
François
F
Tron
Jean
J
Costentin
Tomas
T
Hökfelt
Pierre
P
Déchelotte
Sergueï O
SO
Fetissov
D000818:Animals; D000915:Antibody Affinity; D001007:Anxiety / Q000276:immunology*; D001066:Appetite; D001323:Autoantibodies / Q000096:biosynthesis* / Q000502:physiology; D004435:Eating / Q000276:immunology*; D005260:Female; D007031:Hypothalamus / Q000276:immunology / Q000378:metabolism; D007116:Immunization, Passive; D018782:Maze Learning; D009478:Neuropeptide Y / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000276:immunology* / Q000523:psychology; D000521:alpha-MSH / Q000097:blood / Q000276:immunology*
D001323:Autoantibodies; D009478:Neuropeptide Y; D012333:RNA, Messenger; D000521:alpha-MSH