AA肉鸡和如皋黄鸡海马和下丘脑GR和FKBP5的表达及其与应激敏感性的关系

doi:10.11843/j.issn.0366-6964.2023.11.030

摘要/Abstract

摘要： 旨在探究肉鸡海马和下丘脑糖皮质激素受体(glucocorticoid receptor,GR)及其负反馈因子FK-506结合蛋白5(FK-506 binding protein,FKBP5)的表达是否与应激敏感性有关。选用35日龄的AA肉鸡和如皋黄鸡,连续10 d皮下注射皮质酮(corticosterone,CORT),建立慢性应激模型。对应激后AA肉鸡和如皋黄鸡的体重、采食量、行为、血浆生化指标等进行检测,比较应激敏感性的差异。通过qPCR和Western blot检测海马和下丘脑GR和FKBP5的表达,并与血浆CORT水平进行相关分析。结果表明:1)AA肉鸡在CORT处理后体重显著降低,紧张性不动持续时间和血浆CORT水平均显著增加,但如皋黄鸡变化均不显著;AA肉鸡和如皋黄鸡血液异嗜性粒细胞/淋巴细胞比率在CORT处理后均显著上调,但AA肉鸡显著高于如皋黄鸡。2)基础状态下,如皋黄鸡海马和下丘脑GR蛋白表达量显著高于AA肉鸡;CORT处理导致AA肉鸡和如皋黄鸡海马和下丘脑GR蛋白表达显著下调,但应激后如皋黄鸡GR蛋白表达量仍显著高于AA肉鸡。3)CORT诱导AA肉鸡海马和下丘脑FKBP5 mRNA 和蛋白表达均显著上调,而如皋黄鸡海马和下丘脑FKBP5的上调只发生在蛋白水平,mRNA的表达量没有变化;应激后AA肉鸡FKBP5的蛋白表达量显著高于如皋黄鸡。4)血浆CORT水平与海马和下丘脑中GR蛋白表达量呈负相关,与FKBP5蛋白表达量呈正相关;海马和下丘脑中GR与FKBP5的蛋白表达量呈负相关。以上结果表明,AA肉鸡和如皋黄鸡应激敏感性的差异与海马和下丘脑GR和FKBP5的表达及其调控有关。

关键词: 肉鸡, 应激, 海马, 下丘脑, 糖皮质激素受体, FK-506结合蛋白5

Abstract: This study was conducted to investigate whether the expression of glucocorticoid receptor (GR) and FK-506 binding protein 5 (FKBP5) in hippocampus and hypothalamus of broiler chickens is related to stress sensitivity. Arbor Acres (AA) and Rugao yellow (Rugao) broiler chickens at 35 days of age were injected subcutaneously with corticosterone (CORT) for 10 consecutive days to establish a chronic stress model. The body weight, feed intake, behavior and plasma biochemical indexes of the two lines of chickens were detected, and the differences in stress sensitivity were compared. The expression of GR and FKBP5 in hippocampus and hypothalamus were detected by qPCR and Western blot, and their correlation with plasma CORT levels was analyzed. The results showed as follows: 1) After CORT treatment, the body weight of AA decreased significantly, the tonic immobility (TI) duration and plasma CORT level increased significantly, but there was no significant change in Rugao. CORT treatment resulted in increased heterophil/lymphocyte (H/L) ratio in blood of both AA and Rugao, yet H/L ratio was significantly higher in AA than in Rugao. 2) The basal level of GR protein expression in hippocampus and hypothalamus was significantly higher in Rugao than that in AA; The protein expression of GR was significantly down-regulated after CORT treatment, but Rugao still showed significantly higher GR protein than AA after stress. 3) CORT significantly up-regulated FKBP5 expression at both mRNA and protein levels in hippocampus and hypothalamus of AA, while the FKBP5 up-regulation in hippocampus and hypothalamus of Rugao only occurred at the protein level. FKBP5 protein expression was significantly in AA than in Rugao after stress. 4) Plasma CORT level was negatively correlated with GR protein expression in hippocampus and hypothalamus, and positively correlated with FKBP5 protein expression. GR was negatively correlated with FKBP5 protein expression in hippocampus and hypothalamus. These results indicate that AA and Rugao have different stress sensitivity, and the expression levels of GR and FKBP5 in hippocampus and hypothalamus are related to stress sensitivity.

Key words: broiler chicken, stress, hippocampus, hypothalamus, glucocorticoid receptor, FK-506 binding protein 5

中图分类号:

S852.21

刘杰, 丛玮, 赵敏蝶, 赵茹茜. AA肉鸡和如皋黄鸡海马和下丘脑GR和FKBP5的表达及其与应激敏感性的关系[J]. 畜牧兽医学报, 2023, 54(11): 4766-4776.

LIU Jie, CONG Wei, ZHAO Mindie, ZHAO Ruqian. Expression of GR and FKBP5 in Hippocampus and Hypothalamus of Arbor Acres and Rugao Yellow Broiler Chickens and Its Relationship with Stress Sensitivity[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(11): 4766-4776.

参考文献 41

[1]	ADU-ASIAMAH P, ZHANG Y, AMOAH K,et al. Evaluation of physiological and molecular responses to acute heat stress in two chicken breeds [J]. Animal,2021,15(2):100106.
[2]	RIMOLDI S,LASAGNA E,SARTI F M,et al. Expression profile of six stress-related genes and productive performances of fast and slow growing broiler strains reared under heat stress conditions [J]. Meta Gene,2015,6:17-25.
[3]	XIE S,YANG X,GAO Y,et al. Performance differences of Rhode Island Red, Bashang Long-tail chicken, and their reciprocal crossbreds under natural cold stress [J]. Asian-Australas J Anim Sci,2017,30(10):1507-1514.
[4]	LØTVEDT P, FALLAHSHAHROUDI A, BEKTIC L, et al. Chicken domestication changes expression of stress-related genes in brain, pituitary and adrenals [J]. Neurobiol Stress,2017,7:113-121.
[5]	MCEWEN B S. Protective and damaging effects of stress mediators [J]. N Engl J Med,1998,338(3):171-179.
[6]	SMITH S M, VALE W W. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress [J]. Dialogues Clin Neurosci,2006,8(4):383-395.
[7]	ERICSSON M,FALLAHSHAROUDI A,BERGQUIST J,et al. Domestication effects on behavioural and hormonal responses to acute stress in chickens [J]. Physiol Behav,2014,133:161-169.
[8]	GRAD I, PICARD D. The glucocorticoid responses are shaped by molecular chaperones [J]. Mol Cell Endocrinol,2007,275(1-2):2-12.
[9]	WOCHNIK G M,RVEGG J,ABEL G A,et al. FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells [J]. J Biol Chem,2005,280(6):4609-4616.
[10]	DENNY W B,VALENTINE D L,REYNOLDS P D,et al. Squirrel monkey immunophilin FKBP51 is a potent inhibitor of glucocorticoid receptor binding [J]. Endocrinology,2000,141(11):4107-4113.
[11]	HUBLER T R, SCAMMELL J G. Intronic hormone response elements mediate regulation of FKBP5 by progestins and glucocorticoids [J]. Cell Stress Chaperones,2004,9(3):243-252.
[12]	BINDER E B. The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders [J]. Psychoneuroendocrinology,2009,34:S186-S195.
[13]	KLENGEL T,MEHTA D,ANACKER C,et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions [J]. Nat Neurosci,2013,16(1):33-41.
[14]	GERRITSEN L,MILANESCHI Y,VINKERS C H,et al. HPA axis genes, and their interaction with childhood maltreatment, are related to cortisol levels and stress-related phenotypes [J]. Neuropsychopharmacology,2017,42(12):2446-2455.
[15]	GUIDOTTI G,CALABRESE F,ANACKER C,et al. Glucocorticoid receptor and FKBP5 expression is altered following exposure to chronic stress: modulation by antidepressant treatment [J]. Neuropsychopharmacology,2013,38(4):616-627.
[16]	QIU B,ZHONG Z,RIGHTER S,et al. FKBP51 modulates hippocampal size and function in post-translational regulation of Parkin [J]. Cell Mol Life Sci,2022,79(3):175.
[17]	CODAGNONE M G,KARA N,RATSIKA A,et al. Inhibition of FKBP51 induces stress resilience and alters hippocampal neurogenesis [J]. Mol Psychiatry,2022,27(12):4928-4938.
[18]	SCHARF S H,LIEBL C,BINDER E B,et al. Expression and regulation of the Fkbp5 gene in the adult mouse brain [J]. PLoS One,2011,6(2):e16883.
[19]	ZIMMER C,HANSON H E, MARTIN L B. FKBP5 expression is related to HPA flexibility and the capacity to cope with stressors in female and male house sparrows [J]. Horm Behav,2021,135:105038.
[20]	DUAN Y,FU W,WANG S,et al. Cholesterol deregulation induced by chronic corticosterone (CORT) stress in pectoralis major of broiler chickens [J]. Comp Biochem Physiol A Mol Integr Physiol,2014,176:59-64.
[21]	HU Y,FENG Y,ZHANG L,et al. GR-mediated FTO transactivation induces lipid accumulation in hepatocytes via demethylation of m(6)A on lipogenic mRNAs [J]. RNA Biol,2020,17(7):930-942.
[22]	GRIFFIN C,FLOURIOT G,SHARP P,et al. Distribution analysis of the two chicken estrogen receptor-alpha isoforms and their transcripts in the hypothalamus and anterior pituitary gland [J]. Biol Reprod,2001,65(4):1156-1163.
[23]	GUPTA S K,BEHERA K,PRADHAN C R,et al. Studies of the macroscopic and microscopic morphology (hippocampus) of brain in Vencobb broiler [J]. Vet World,2016,9(5):507-511.
[24]	YAN C,XIAO J,CHEN D,et al. Feed restriction induced changes in behavior, corticosterone, and microbial programming in slow- and fast-growing chicken breeds [J]. Animals (Basel),2021,11(1):141.
[25]	VACCARO L A,PORTER T E and ELLESTAD L E. Effects of genetic selection on activity of corticotropic and thyrotropic axes in modern broiler chickens [J]. Domest Anim Endocrinol,2022,78:106649.
[26]	FANATICO A C,PILLAI P B,EMMERT J L,et al. Meat quality of slow- and fast-growing chicken genotypes fed low-nutrient or standard diets and raised indoors or with outdoor access [J]. Poult Sci,2007,86(10):2245-2255.
[27]	FANATICO A C,PILLAI P B,HESTER P Y,et al. Performance, livability, and carcass yield of slow- and fast-growing chicken genotypes fed low-nutrient or standard diets and raised indoors or with outdoor access [J]. Poult Sci,2008,87(6):1012-1021.
[28]	SOLEIMANI A F,ZULKIFLI I,OMAR A R,et al. Physiological responses of 3 chicken breeds to acute heat stress [J]. Poult Sci,2011,90(7):1435-1440.
[29]	XU Y,LAI X,LI Z,et al. Effect of chronic heat stress on some physiological and immunological parameters in different breed of broilers [J]. Poult Sci,2018,97(11):4073-4082.
[30]	CAMPLER M,JöNGREN M, JENSEN P. Fearfulness in red junglefowl and domesticated White Leghorn chickens [J]. Behav Processes,2009,81(1):39-43.
[31]	KHAN M S,SHIGEOKA C,TAKAHARA Y,et al. Ontogeny of the corticotrophin-releasing hormone system in slow- and fast-growing chicks (Gallus gallus) [J]. Physiol Behav,2015,151:38-45.
[32]	YUAN L,NI Y,BARTH S,et al. Layer and broiler chicks exhibit similar hypothalamic expression of orexigenic neuropeptides but distinct expression of genes related to energy homeostasis and obesity [J]. Brain Res,2009,1273:18-28.
[33]	PRAJAPATI S K,DANGI D S, KRISHNAMURTHY S. Repeated caffeine administration aggravates post-traumatic stress disorder-like symptoms in rats [J]. Physiol Behav,2019,211:112666.
[34]	DANAN D,TODDER D,ZOHAR J,et al. Is PTSD-phenotype associated with HPA-axis sensitivity? Feedback inhibition and other modulating factors of glucocorticoid signaling dynamics [J]. Int J Mol Sci,2021,22(11):6050.
[35]	AHMED A A,MA W,NI Y,et al. Embryonic exposure to corticosterone modifies aggressive behavior through alterations of the hypothalamic pituitary adrenal axis and the serotonergic system in the chicken [J]. Horm Behav,2014,65(2):97-105.
[36]	CRIADO-MARRERO M,REIN T,BINDER E B,et al. Hsp90 and FKBP51: complex regulators of psychiatric diseases [J]. Philos Trans R Soc Lond B Biol Sci,2018,373(1738):20160532.
[37]	LI H,SU P,LAI T K,et al. The glucocorticoid receptor-FKBP51 complex contributes to fear conditioning and posttraumatic stress disorder [J]. J Clin Invest,2020,130(2):877-889.
[38]	MERKULOV V M,MERKULOVA T I and BONDAR N P. Mechanisms of brain glucocorticoid resistance in stress-induced psychopathologies [J]. Biochemistry (Mosc),2017,82(3):351-365.
[39]	CASTRO-VALE I,VAN ROSSUM E F,MACHADO J C,et al. Genetics of glucocorticoid regulation and posttraumatic stress disorder--What do we know? [J]. Neurosci Biobehav Rev,2016,63:143-157.
[40]	MENDONÇA M S, MANGIAVACCHI P M, RIOS Á F L. Regulatory functions of FKBP5 intronic regions associated with psychiatric disorders [J]. J Psychiatr Res,2021,143:1-8.
[41]	REYER H,PONSUKSILI S,WIMMERS K,et al. Association of N-terminal domain polymorphisms of the porcine glucocorticoid receptor with carcass composition and meat quality traits [J]. Anim Genet,2014,45(1):125-129.