Development of Activity-based Anorexia Requires PKC-δ Neurons in Two Central Extended Amygdala Nuclei

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2024 Mar 9

PMID 38460131

Authors

Wesley Ilana Schnapp

Jungmin Kim

Yong Wang

Sayujya Timilsena

Caohui Fang

Haijiang Cai

Affiliations

Soon will be listed here.

Abstract

Anorexia nervosa (AN) is a serious psychiatric disease, but the neural mechanisms underlying its development are unclear. A subpopulation of amygdala neurons, marked by expression of protein kinase C-delta (PKC-δ), has previously been shown to regulate diverse anorexigenic signals. Here, we demonstrate that these neurons regulate development of activity-based anorexia (ABA), a common animal model for AN. PKC-δ neurons are located in two nuclei of the central extended amygdala (EAc): the central nucleus (CeA) and oval region of the bed nucleus of the stria terminalis (ovBNST). Simultaneous ablation of CeA and ovBNST neurons prevents ABA, but ablating PKC-δ neurons in the CeA or ovBNST alone is not sufficient. Correspondingly, PKC-δ neurons in both nuclei show increased activity with ABA development. Our study shows how neurons in the amygdala regulate ABA by impacting both feeding and wheel activity behaviors and support a complex heterogeneous etiology of AN.

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References

Klenotich S, Ho E, McMurray M, Server C, Dulawa S . Dopamine D2/3 receptor antagonism reduces activity-based anorexia. Transl Psychiatry. 2015; 5:e613. PMC: 4564564. DOI: 10.1038/tp.2015.109. View

Welch A, Zhang J, Lyu J, McMurray M, Javitch J, Kellendonk C . Dopamine D2 receptor overexpression in the nucleus accumbens core induces robust weight loss during scheduled fasting selectively in female mice. Mol Psychiatry. 2019; 26(8):3765-3777. PMC: 7305037. DOI: 10.1038/s41380-019-0633-8. View

Mistlberger R . Food as circadian time cue for appetitive behavior. F1000Res. 2020; 9. PMC: 6993826. DOI: 10.12688/f1000research.20829.1. View

Francois M, Zeltser L . Rethinking the Approach to Preclinical Models of Anorexia Nervosa. Curr Psychiatry Rep. 2022; 24(1):71-76. PMC: 8898221. DOI: 10.1007/s11920-022-01319-2. View

Sternson S, Eiselt A . Three Pillars for the Neural Control of Appetite. Annu Rev Physiol. 2016; 79:401-423. DOI: 10.1146/annurev-physiol-021115-104948. View

Chowdhury T, Chen Y, Aoki C . Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa. J Vis Exp. 2015; (105):e52927. PMC: 4692666. DOI: 10.3791/52927. View

Manzanares G, Brito-da-Silva G, Gandra P . Voluntary wheel running: patterns and physiological effects in mice. Braz J Med Biol Res. 2018; 52(1):e7830. PMC: 6301263. DOI: 10.1590/1414-431X20187830. View

Hebebrand J, Exner C, Hebebrand K, Holtkamp C, Casper R, Remschmidt H . Hyperactivity in patients with anorexia nervosa and in semistarved rats: evidence for a pivotal role of hypoleptinemia. Physiol Behav. 2003; 79(1):25-37. DOI: 10.1016/s0031-9384(03)00102-1. View

Ip C, Zhang L, Farzi A, Qi Y, Clarke I, Reed F . Amygdala NPY Circuits Promote the Development of Accelerated Obesity under Chronic Stress Conditions. Cell Metab. 2019; 30(1):111-128.e6. DOI: 10.1016/j.cmet.2019.04.001. View

10.

Ross R, Mandelblat-Cerf Y, Verstegen A . Interacting Neural Processes of Feeding, Hyperactivity, Stress, Reward, and the Utility of the Activity-Based Anorexia Model of Anorexia Nervosa. Harv Rev Psychiatry. 2016; 24(6):416-436. PMC: 5485261. DOI: 10.1097/HRP.0000000000000111. View

11.

Perrin J, Segall L, Harbour V, Woodside B, Amir S . The expression of the clock protein PER2 in the limbic forebrain is modulated by the estrous cycle. Proc Natl Acad Sci U S A. 2006; 103(14):5591-6. PMC: 1459398. DOI: 10.1073/pnas.0601310103. View

12.

Mattar L, Thiebaud M, Huas C, Cebula C, Godart N . Depression, anxiety and obsessive-compulsive symptoms in relation to nutritional status and outcome in severe anorexia nervosa. Psychiatry Res. 2012; 200(2-3):513-7. DOI: 10.1016/j.psychres.2012.04.032. View

13.

Achamrah N, Nobis S, Goichon A, Breton J, Legrand R, do Rego J . Sex differences in response to activity-based anorexia model in C57Bl/6 mice. Physiol Behav. 2016; 170:1-5. DOI: 10.1016/j.physbeh.2016.12.014. View

14.

Jagielska G, Kacperska I . Outcome, comorbidity and prognosis in anorexia nervosa. Psychiatr Pol. 2017; 51(2):205-218. DOI: 10.12740/PP/64580. View

15.

Hardaway J, Halladay L, Mazzone C, Pati D, Bloodgood D, Kim M . Central Amygdala Prepronociceptin-Expressing Neurons Mediate Palatable Food Consumption and Reward. Neuron. 2019; 102(5):1037-1052.e7. PMC: 6750705. DOI: 10.1016/j.neuron.2019.03.037. View

16.

Amir S, Stewart J . Behavioral and hormonal regulation of expression of the clock protein, PER2, in the central extended amygdala. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33(8):1321-8. DOI: 10.1016/j.pnpbp.2009.04.003. View

17.

Hardaway J, Crowley N, Bulik C, Kash T . Integrated circuits and molecular components for stress and feeding: implications for eating disorders. Genes Brain Behav. 2014; 14(1):85-97. PMC: 4465370. DOI: 10.1111/gbb.12185. View

18.

Kron L, Katz J, Gorzynski G, Weiner H . Hyperactivity in anorexia nervosa: a fundamental clinical feature. Compr Psychiatry. 1978; 19(5):433-40. DOI: 10.1016/0010-440x(78)90072-x. View

19.

Routtenberg A, Kuznesof A . Self-starvation of rats living in activity wheels on a restricted feeding schedule. J Comp Physiol Psychol. 1967; 64(3):414-21. DOI: 10.1037/h0025205. View

20.

Beneke W, Schulte S, Vander Tuig J . An analysis of excessive running in the development of activity anorexia. Physiol Behav. 1995; 58(3):451-7. DOI: 10.1016/0031-9384(95)00083-u. View