Fasting alters p75NTR and AgRP mRNA expression in rat olfactory bulb and hippocampus

Abstract

Classic non-homeostatic structures involved in food intake regulation are reciprocally influenced by metabolic signals. Orexigenic peptides expressed in the olfactory bulb (OB) and hippocampus (HP) modulate olfactory processing and memory, respectively. Hypothalamic circuits also modulate feeding behavior by activating and releasing Agouti-related peptide (AgRP) in response to orexigenic signals. An adequate response to fasting requires the expression of p75 neurotrophin receptor (p75NTR) in AgRP neurons. The present study aimed to determine whether there is a role for p75NTR and AgRP in the OB and HP on the feeding behavior of fasted rats. A group of fasted rats (FG) was confronted with a decision-making paradigm in a T-maze containing a standard chow pellet (CP), and the same pellet coated with a phenolic-rich avocado paste extract (AVO) on either end; their OB and HP were then analyzed with histological and molecular tools. FG rats had briefer feeding latencies, as compared to control rats fed ad libitum (median latencies: 55.4 vs 191.7 min, p = 0.032). They also had reduced cell counts in both brain structures, as compared to satiated rats. AgRP mRNA was not expressed in the HP of either group, however, it was found in the OB. p75NTR mRNA was expressed in both brain structures of FG rats. These results suggest that contrasting metabolic states (fasted or satiated) motivate different feeding responses, which are influenced by p75NTR and AgRP mRNA expression in non-homeostatic food intake brain structures.

Keywords

• Food intake regulation
• Appetitive behavior
• Avocado
• p75 neurotrophin receptor
• Agouti-related peptide

References

1. Abbate F, Guerrera MC, Montalbano G, Levanti MB, Germanà GP, Navarra M, Laurà R, Vega JA, Ciriaco E, Germanà A. (2014). Expression and anatomical distribution of TrkB in the encephalon of the adult zebrafish (Danio rerio). Neurosci Lett. 563:66–69. https://doi.org/10.1016/j.neulet.2014.01.031.
2. Aguayo-Del Castillo A, Sánchez-Castillo H, Casasola-Castro C. (2016). Alternancia espacial: el laberinto en forma de T, sus procedimientos y procesos. Rev Mex Neuroci. 17(5): 36-48. http://previous.revmexneurociencia.com/wp-content/uploads/2016/10/RevMexNeu-No-3-May-Jun-2016-36-48-R.pdf
3. Andermann ML, Lowell BB. (2017). Toward a Wiring Diagram Understanding of Appetite Control. Neuron. 95(4):757–778. https://doi.org/10.1016/j.neuron.2017.06.014.
4. Baeza-Raja B, Sachs BD, Li P, Christian F, Vagena E, Davalos D, Le Moan N, Ryu JK, Sikorski SL, Chan JP, Scadeng M, Taylor SS, Houslay MD, Baillie GS, Saltiel AR, Olefsky JM, Akassoglou K. (2016). p75 Neurotrophin Receptor Regulates Energy Balance in Obesity. Cell Rep. 14(2):255–268. https://doi.org/10.1016/j.celrep.2015.12.028.
5. Bake T, Edvardsson CE, Cummings CJ, Dickson SL. (2019). Ghrelin’s effects on food motivation in rats are not limited to palatable foods. J Neuroendocrinol. 31(7): e12665. https://doi.org/10.1111/jne.12665.
6. Begg DP, Woods SC. (2013). The endocrinology of food intake. Nat Rev Endocrinol. 9(10):584-97. https://doi.org/10.1038/nrendo.2013.136.
7. Benelam B. (2009). Satiation, satiety and their effects on eating behaviour. Nutr Bull. 34(2):126–173. https://doi.org/10.1111/j.1467-3010.2009.01753.x.
8. Berthoud H-R, Münzberg H, Morrison CD. (2017). Blaming the Brain for Obesity: Integration of Hedonic and Homeostatic Mechanisms. Gastroenterology. 152(7):1728-1738. https://doi.org/10.1053/j.gastro.2016.12.050.

9. Boswell T, Li Q, Takeuchi S. (2002). Neurons expressing neuropeptide Y mRNA in the infundibular hypothalamus of Japanese quail are activated by fasting and co-express agouti-related protein mRNA. Mol Brain Res. 100(1-2):31–42. https://doi.org/10.1016/S0169-328X(02)00145-6.
10. Broberger C, Johansen J, Johansson C, Schalling M, Hökfelt T. (1998) The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. Proc Natl Acad Sci U S A. 95(25):15043–15048. https://doi.org/10.1073/pnas.95.25.15043.
11. Bunner W, Landry T, Laing BT, Li P, Rao Z, Yuan Y, Huang H. (2020). ARCAgRP/NPY Neuron Activity Is Required for Acute Exercise-Induced Food Intake in Un-Trained Mice. Front Physiol. 11:411. https://doi.org/10.3389/fphys.2020.00411.
12. Catts VS, Al-Menhali N, Burne THJ, Colditz MJ, Coulson EJ. (2008). The p75 neurotrophin receptor regulates hippocampal neurogenesis and related behaviours. Eur J Neurosci. 28(5):883–892. https://doi.org/10.1111/j.1460-9568.2008.06390.x.
13. Chao MV. (2003). Neurotrophins and their receptors: A convergence point for many signalling pathways. Nat Rev Neurosci. 4(4):299–309. https://doi.org/10.1038/nrn1078.
14. Corella-Salazar DA, Domínguez-Avila JA, Montiel-Herrera M, Astiazaran-Garcia H, Salazar-López NJ, Serafín-García MS, Olivas-Orozco GI, Molina-Corral FJ, González-Aguilar GA. (2021). Sub-chronic consumption of a phenolic-rich avocado paste extract induces GLP-1-, leptin-, and adiponectin-mediated satiety in Wistar rats. J Food Biochem. 45(11):e13957. https://doi.org/10.1111/jfbc.13957.
15. Dornellas APS, Boldarine VT, Pedroso AP, Carvalho LOT, de Andrade IS, Vulcani-Freitas TM, dos Santos CCC, do Nascimento CM da PO, Oyama LM, Ribeiro EB. (2018). High-Fat Feeding Improves Anxiety-Type Behavior Induced by Ovariectomy in Rats. Front Neurosci. 12:557. https://doi.org/10.3389/fnins.2018.00557.
16. Fiszman S, Tarrega A. (2017). Expectations of food satiation and satiety reviewed with special focus on food properties. Food Funct. 8:2686–2697. https://doi.org/10.1039/C7FO00307B.
17. Francois M, Canal Delgado I, Shargorodsky N, Leu C-S, Zeltser L. (2022). Assessing the effects of stress on feeding behaviors in laboratory mice. eLife. 11:e70271. https://doi.org/10.7554/eLife.70271.
18. Goldstein N, McKnight AD, Carty JRE, Arnold M, Betley JN, Alhadeff AL. (2021). Hypothalamic detection of macronutrients via multiple gut-brain pathways. Cell Metab. 33(3):676-687.e5. https://doi.org/10.1016/j.cmet.2020.12.018.
19. Goldstone AP, Prechtl de Hernandez CG, Beaver JD, Muhammed K, Croese C, Bell G, Durighel G, Hughes E, Waldman AD, Frost G, Bell JD. (2009). Fasting biases brain reward systems towards high-calorie foods. Eur J Neurosci. 30(8):1625–1635. https://doi.org/10.1111/j.1460-9568.2009.06949.x.
20. Hashimoto K, Koizumi H, Nakazato M, Shimizu E, Iyo M. (2005). Role of brain-derived neurotrophic factor in eating disorders: Recent findings and its pathophysiological implications. Prog Neuropsychopharmacol Biol Psychiatry. 29(4):499–504. https://doi.org/10.1016/j.pnpbp.2005.01.007.
21. Haskell-Luevano C, Chen P, Li C, Chang K, Smith MS, Cameron JL, Cone RD. (1999). Characterization of the Neuroanatomical Distribution of Agouti-Related Protein Immunoreactivity in the Rhesus Monkey and the Rat. Endocrinology. 140(3):1408-15. https://doi.org/10.1210/endo.140.3.6544.
22. Hernández Ruiz de Eguilaz M, Martínez de Morentin Aldabe B, Almiron-Roig E, Pérez-Diez S, San Cristóbal Blanco R, Navas-Carretero S, Martínez JA. (2018). Influencia multisensorial sobre la conducta alimentaria: ingesta hedónica. Endocrinol Diabetes Nutr. 65(2):114–125. https://doi.org/10.1016/j.endinu.2017.09.008.
23. Kernie SG, Liebl DJ, Parada LF. (2000). BDNF regulates eating behavior and locomotor activity in mice. EMBO J. 19(6):1290–1300. https://doi.org/10.1093/emboj/19.6.1290.
24. Liu CM, Kanoski SE. (2018). Homeostatic and non-homeostatic controls of feeding behavior: Distinct vs. common neural systems. Physiol Behav. 193(Pt B):223-231. https://doi.org/10.1016/j.physbeh.2018.02.011.
25. Long J-Y, Jiang W, Xia H-B, Fu J-Y, Lu P, Hu F, Feng W-C, Sun W-W, Gao M-M, Yi Y-H, Long Y-S. (2020). FMRP-absence-induced up-regulation of hypothalamic MAP1B expression decreases AgRP level linking with reduces in food intake and body weight. Neurochem Int. 140:104847. https://doi.org/10.1016/j.neuint.2020.104847.
26. Lyons WE, Mamounas LA, Ricaurte GA, Coppola V, Reid SW, Bora SH, Wihler C, Koliatsos VE, Tessarollo L. (1999). Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc Natl Acad Sci. 96(26):15239–15244. https://doi.org/10.1073/pnas.96.26.15239.
27. Paul A, Chaker Z, Doetsch F. (2017). Hypothalamic regulation of regionally distinct adult neural stem cells and neurogenesis. Science. 356(6345):1383–1386. https://doi.org/10.1126/science.aal3839.
28. Podyma B, Johnson D, Sipe L, Battin K, Remcho P, Deppmann CD, Güler AD. (2020a). SAT-602 Hypothalamic P75 Neurotrophin Receptor Regulates Homeostatic Feeding and Food Anticipation. J Endocr Soc. 4(1). https://doi.org/10.1210/jendso/bvaa046.520.
29. Podyma B, Johnson D-A, Sipe L, Remcho TP, Battin K, Liu Y, Yoon SO, Deppmann CD, Güler AD. (2020b). The p75 neurotrophin receptor in AgRP neurons is necessary for homeostatic feeding and food anticipation. eLife. 9:e52623. https://doi.org/10.7554/eLife.52623.
30. Rios M, Fan G, Fekete C, Kelly J, Bates B, Kuehn R, Lechan RM, Jaenisch R. (2001). Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol Endocrinol Baltim Md. 15(10):1748–1757. https://doi.org/10.1210/mend.15.10.0706.
31. Robertson B-A, Rathbone L, Cirillo G, D’Eath RB, Bateson M, Boswell T, Wilson PW, Dunn IC, Smulders TV. (2017). Food restriction reduces neurogenesis in the avian hippocampal formation. PLOS ONE. 12(12):e0189158. https://doi.org/10.1371/journal.pone.0189158.
32. Rossi MA, Stuber GD. (2018). Overlapping Brain Circuits for Homeostatic and Hedonic Feeding. Cell Metab. 27(1):42–56. https://doi.org/10.1016/j.cmet.2017.09.021.
33. Singh M, Thrimawithana T, Shukla R, Adhikari B. (2020). Managing obesity through natural polyphenols: A review. Future Foods. 1–2:1–50. https://doi.org/10.1016/j.fufo.2020.100002.
34. Smiljanic K, Pesic V, Mladenovic Djordjevic A, Pavkovic Z, Brkic M, Ruzdijic S, Kanazir S. (2015). Long-term dietary restriction differentially affects the expression of BDNF and its receptors in the cortex and hippocampus of middle-aged and aged male rats. Biogerontology. 16(1):71–83. https://doi.org/10.1007/s10522-014-9537-9.
35. Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, Tecott LH, Reichardt LF. (2003). Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci. 6(7):736–742. https://doi.org/10.1038/nn1073.
36. Zucoloto FS. (2011). Evolution of the human feeding behavior. Psychol Neurosci. 4(1):131–141. https://doi.org/10.3922/j.psns.2011.1.015.
37. Zuloaga KL, Temple S. (2017). Appetite for Neurogenesis. Dev Cell. 42(3):207–209. https://doi.org/10.1016/j.devcel.2017.07.018.
38. Zuñiga-Martínez BS, Domínguez-Avila JA, Wall-Medrano A, Ayala-Zavala JF, Hernández-Paredes J, Salazar-López NJ, Villegas-Ochoa MA, González-Aguilar GA. (2021). Avocado paste from industrial byproducts as an unconventional source of bioactive compounds: characterization, in vitro digestion and in silico interactions of its main phenolics with cholesterol. J Food Meas Charact. 15:5460–5476. https://doi.org/10.1007/s11694-021-01117-z.