Diminished feeding responsiveness to orexin A (hypocretin 1) in aged rats is accompanied by decreased neuronal activation

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2005-08, Vol.289 (2), p.R359-R366
• Main Authors: Kotz, Catherine M, Mullett, Mary A, Wang, ChuanFeng
• Format: Article
• Language: English
• Subjects: Aging - physiology; Animals; Brain - cytology; Brain - metabolism; Eating - drug effects; Eating - physiology; Immunohistochemistry; Intracellular Signaling Peptides and Proteins - pharmacology; Male; Mediodorsal Thalamic Nucleus - metabolism; Neurons - metabolism; Neuropeptides - pharmacology; Orexins; Paraventricular Hypothalamic Nucleus - metabolism; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Inbred F344; Time Factors
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00717.2004

1 Veterans Affairs Medical Center and 2 Minnesota Obesity Center, Minneapolis; and Departments of Food Science and 3 Nutrition and 4 Medicine, University of Minnesota, Saint Paul, Minnesota Submitted 21 October 2004 ; accepted in final form 28 April 2005 Orexin A is produced in caudal lateral, posterior, perifornical, and dorsomedial hypothalamic areas. Orexin A in the rostro-dorsal lateral hypothalamic area (rLHa) stimulates feeding and activates several feeding-regulatory brain areas. We hypothesized that aging diminishes feeding and c-Fos-immunoreactivity (c-Fos-ir; marker of neuronal activation) response to orexin A. Young (3 mo), middle-aged (12 mo), and old (24 mo) male Fischer 344 rLHa-cannulated rats were injected with orexin A (0.5, 1, and 2 nmol). Food intake was measured at 1, 2, and 4 h. c-Fos-ir in hypothalamic, limbic, and hindbrain regions was measured in two additional sets of rLHa-orexin A injected rats. In a separate study, orexin A effects on feeding and c-Fos-ir were measured in 6-mo-old rats. Orexin A significantly elevated feeding in rats aged 3, 6, and 12 mo in the 0–1 and 1–2- h time intervals, whereas in old rats this was significant in the 1–2 h time interval only. At 1 h, 6–8 (of 14) brain areas showed elevated c-Fos-ir in response to orexin A in 3- and 6-mo-old rats, but 24-mo-old rats exhibited attenuated or absent c-Fos-ir response in all brain regions except the hypothalamic paraventricular nucleus (PVN) and rostral nucleus of the solitary tract (rNTS). Orexin A did not elevate c-Fos-ir in 3-mo-old rats at 2 h after injection, whereas the PVN and mediodorsal thalamic nucleus (MD) showed elevated c-Fos-ir at 2 h in 24-mo-old rats. These data suggest that delayed and diminished feeding responses in old animals may be due to ineffective neural signaling and implicate the orexin A network as one feeding system affected by aging. feeding behavior; sleep; lateral hypothalamus; aging; c-Fos-immunoreactivity Address for reprint requests and other correspondence: Catherine Kotz, Veterans Affairs Medical Center, GRECC (11G), One Veterans Drive, Minneapolis, MN 55417 (E-mail: kotzx004{at}umn.edu )