Nesfatin-1 Injected Intracerebroventricularly Increases Anxiety, Depression-Like Behavior, and Anhedonia in Normal Weight Rats

Overview

Journal Nutrients

Date 2018 Dec 6

PMID 30513901

Citations 5

Authors

Stephanie Gladys Kuhne

Martha Anna Schalla

Tiemo Friedrich

Peter Kobelt

Miriam Goebel-Stengel

Melissa Long

Marion Rivalan

York Winter

Matthias Rose

Andreas Stengel

Affiliations

Soon will be listed here.

Abstract

Nesfatin-1 is a well-established anorexigenic peptide. Recent studies indicated an association between nesfatin-1 and anxiety/depression-like behavior. However, it is unclear whether this effect is retained in obesity. The aim was to investigate the effect of nesfatin-1-the active core of nesfatin-1-on anxiety and depression-like behavior in normal weight (NW) and diet-induced (DIO) obese rats. Male rats were intracerebroventricularly (ICV) cannulated and received nesfatin-1 (0.1, 0.3, or 0.9 nmol/rat) or vehicle 30 min before testing. Nesfatin-1 at a dose of 0.3 nmol reduced sucrose consumption in the sucrose preference test in NW rats compared to vehicle (⁻33%, < 0.05), indicating depression-like/anhedonic behavior. This dose was used for all following experiments. Nesfatin-1 also reduced cookie intake during the novelty-induced hypophagia test (-62%, < 0.05). Moreover, nesfatin-1 reduced the number of entries into the center zone in the open field test (-45%, < 0.01) and the visits of open arms in the elevated zero maze test (-39%, < 0.01) in NW rats indicating anxiety. Interestingly, DIO rats showed no behavioral alterations after the injection of nesfatin-1 ( > 0.05). These results indicate an implication of nesfatin-1 in the mediation of anxiety and depression-like behavior/anhedonia under normal weight conditions, while in DIO rats, a desensitization might occur.

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References

Whishaw I . The laboratory rat, the Pied Piper of twentieth century neuroscience. Brain Res Bull. 2000; 50(5-6):411. DOI: 10.1016/s0361-9230(99)00169-0. View

Prut L, Belzung C . The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol. 2003; 463(1-3):3-33. DOI: 10.1016/s0014-2999(03)01272-x. View

Bourin M, Hascoet M . The mouse light/dark box test. Eur J Pharmacol. 2003; 463(1-3):55-65. DOI: 10.1016/s0014-2999(03)01274-3. View

Davidowa H, Li Y, Plagemann A . Altered neuronal responses to feeding-relevant peptides as sign of developmental plasticity in the hypothalamic regulatory system of body weight. Zh Vyssh Nerv Deiat Im I P Pavlova. 2003; 53(5):663-70. View

Dulawa S, Hen R . Recent advances in animal models of chronic antidepressant effects: the novelty-induced hypophagia test. Neurosci Biobehav Rev. 2005; 29(4-5):771-83. DOI: 10.1016/j.neubiorev.2005.03.017. View

Brenes Saenz J, Villagra O, Fornaguera Trias J . Factor analysis of Forced Swimming test, Sucrose Preference test and Open Field test on enriched, social and isolated reared rats. Behav Brain Res. 2006; 169(1):57-65. DOI: 10.1016/j.bbr.2005.12.001. View

Oh-I S, Shimizu H, Satoh T, Okada S, Adachi S, Inoue K . Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature. 2006; 443(7112):709-12. DOI: 10.1038/nature05162. View

Pan W, Hsuchou H, Kastin A . Nesfatin-1 crosses the blood-brain barrier without saturation. Peptides. 2007; 28(11):2223-8. DOI: 10.1016/j.peptides.2007.09.005. View

Price T, Samson W, Niehoff M, Banks W . Permeability of the blood-brain barrier to a novel satiety molecule nesfatin-1. Peptides. 2007; 28(12):2372-81. DOI: 10.1016/j.peptides.2007.10.008. View

10.

Merali Z, Cayer C, Kent P, Anisman H . Nesfatin-1 increases anxiety- and fear-related behaviors in the rat. Psychopharmacology (Berl). 2008; 201(1):115-23. DOI: 10.1007/s00213-008-1252-2. View

11.

Stengel A, Goebel M, Yakubov I, Wang L, Witcher D, Coskun T . Identification and characterization of nesfatin-1 immunoreactivity in endocrine cell types of the rat gastric oxyntic mucosa. Endocrinology. 2008; 150(1):232-8. PMC: 2630900. DOI: 10.1210/en.2008-0747. View

12.

Merali Z, Hayley S, Kent P, McIntosh J, Bedard T, Anisman H . Impact of repeated stressor exposure on the release of corticotropin-releasing hormone, arginine-vasopressin and bombesin-like peptides at the anterior pituitary. Behav Brain Res. 2008; 198(1):105-12. DOI: 10.1016/j.bbr.2008.10.025. View

13.

Shimizu H, Oh-I S, Hashimoto K, Nakata M, Yamamoto S, Yoshida N . Peripheral administration of nesfatin-1 reduces food intake in mice: the leptin-independent mechanism. Endocrinology. 2009; 150(2):662-71. DOI: 10.1210/en.2008-0598. View

14.

Goebel M, Stengel A, Wang L, Lambrecht N, Tache Y . Nesfatin-1 immunoreactivity in rat brain and spinal cord autonomic nuclei. Neurosci Lett. 2009; 452(3):241-6. PMC: 2674947. DOI: 10.1016/j.neulet.2009.01.064. View

15.

Goebel M, Stengel A, Wang L, Tache Y . Restraint stress activates nesfatin-1-immunoreactive brain nuclei in rats. Brain Res. 2009; 1300:114-24. PMC: 2783213. DOI: 10.1016/j.brainres.2009.08.082. View

16.

Bonnet M, Pecchi E, Trouslard J, Jean A, Dallaporta M, Troadec J . Central nesfatin-1-expressing neurons are sensitive to peripheral inflammatory stimulus. J Neuroinflammation. 2009; 6:27. PMC: 2762958. DOI: 10.1186/1742-2094-6-27. View

17.

Stengel A, Goebel M, Wang L, Rivier J, Kobelt P, Monnikes H . Central nesfatin-1 reduces dark-phase food intake and gastric emptying in rats: differential role of corticotropin-releasing factor2 receptor. Endocrinology. 2009; 150(11):4911-9. PMC: 2775975. DOI: 10.1210/en.2009-0578. View

18.

Stengel A, Goebel M, Wang L, Tache Y . Abdominal surgery activates nesfatin-1 immunoreactive brain nuclei in rats. Peptides. 2009; 31(2):263-70. PMC: 3166548. DOI: 10.1016/j.peptides.2009.11.015. View

19.

Su Y, Zhang J, Tang Y, Bi F, Liu J . The novel function of nesfatin-1: anti-hyperglycemia. Biochem Biophys Res Commun. 2009; 391(1):1039-42. DOI: 10.1016/j.bbrc.2009.12.014. View

20.

Foo K, Brauner H, Ostenson C, Broberger C . Nucleobindin-2/nesfatin in the endocrine pancreas: distribution and relationship to glycaemic state. J Endocrinol. 2009; 204(3):255-63. DOI: 10.1677/JOE-09-0254. View