Glutamate-dependent regulation of food intake is altered with age through changes in NMDA receptor phenotypes on vagal afferent neurons

Abstract

Compared to younger individuals, older human subjects have significantly lower food intakes and an increased satiety response. N-methyl-d-aspartate (NMDA) receptors expressed by vagal afferent neurons originating from nodose ganglia (NG) are involved in modulating the satiety response. The present study investigated how NMDA receptor subunit phenotypes in NG neurons change with age and how these age-related alterations in food intake are modulated by presynaptic NMDA receptors in the NG of male Sprague Dawley rats (six week-old and sixty week-old). Food intake was measured at 30-, 60-, and 120-min following intraperitoneal administration of cholecystokinin (CCK) or the non-competitive NMDA receptor antagonist MK-801. Immunofluorescence was used to determine NMDA receptor subunit expression (NR1, NR2B, NR2C, and NR2D) in the NG. The results showed that, CCK reduced food intake at 30-, 60-, and 120-min post injection in both young and the middle-age animals, with no statistical difference between the groups at 30- and 60-min. In contrast, MK-801 produced an increase in food intake that was significantly higher in middle-age rats compared to young animals at all time points studied. NR1 subunit was expressed by almost all NG neurons in both age groups. In young rats, NR2B, NR2C, and NR2D subunits were expressed in 56.1%, 49.3%, and 13.9% of NG neurons, respectively. In contrast, only 30.3% of the neuronal population in middle-aged rats expressed NR2B subunit immunoreactivity, NR2C was present in 34.1%, and only 10.6% of total neurons expressed the NR2D subunit. In conclusion, glutamate-dependent regulation of food intake is altered with age and one of the potential mechanisms through which this age-related changes in intake occur is changes in NMDA receptor phenotypes on vagal afferent neurons located in NG.