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.
Sinno
Maria Hamze
MH
Digestive System & Nutrition Laboratory (ADEN EA4311), Institute of Biomedical Research, Rouen University & Hospital, IFR23, 76183 Rouen, France.
Do Rego
Jean Claude
JC
Coëffier
Moïse
M
Bole-Feysot
Christine
C
Ducrotté
Philippe
P
Gilbert
Danièle
D
Tron
François
F
Costentin
Jean
J
Hökfelt
Tomas
T
Déchelotte
Pierre
P
Fetissov
Sergueï O
SO
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