Persistent hyperglycemia induced by chronic restraint stress in rat is associated with nucleus tractus solitarius injury

BI Wen-jie ZHENG Xiang*

doi:10.16098/j.issn.0529-1356.2019.04.004

PDF(5581 KB)

Acta Anatomica Sinica ›› 2019, Vol. 50 ›› Issue (4) : 423-430. DOI: 10.16098/j.issn.0529-1356.2019.04.004

Persistent hyperglycemia induced by chronic restraint stress in rat is associated with nucleus tractus solitarius injury

BI Wen-jie¹ ZHENG Xiang^2*

Author information +

History +

Abstract

Objective To investigate the role of anterior part of commissural subnucleus of nucleus tractus solitarius (acNTS) injury in insulin-resistant hyperglycemia during chronic restraint stress (CRS). Methods We produced the CRS models (n=20， a 7-day restraint followed by a 3-day free moving procedure for 40 days) in rats, and detected the parameters related to glucose metabolism. Results The CRS induced a moderate (not higher than 11 mmol/L) and irreversible insulinresistant hyperglycemia in about 1/3 (n=7) of the individuals. CRS-hyperglycemic rats showed a condensed staining of acNTS neurons, and Caspase-3 immunostaining and TUNEL also showed positive, indicating apoptotic changes of acNTS neurons. After acNTS mechanical damage (n=6), the blood glucose level rised gradually, which also led to insulin-resistant hyperglycemia. The characteristics of hyperinsulinemia, increased islet volume, and serum corticosterone levels in acNTS mice were consistent with those of CRS mice. Conclusion The result indicates that during CRS, injury (apoptosis) of glucose-sensitive acNTS neurons causes dysregulation of blood glucose. Restraint stress model has value as a potential application in the study of stress-induced hyperglycemia.

Key words

Chronic restraint stress

/ Insulin-resistant hyperglycemia / Neuron injury / Nucleus tractus solitaries / Enzyme-linked immunosorbent assay / Rat

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

BI Wen-jie ZHENG Xiang. Persistent hyperglycemia induced by chronic restraint stress in rat is associated with nucleus tractus solitarius injury[J]. Acta Anatomica Sinica. 2019, 50(4): 423-430 https://doi.org/10.16098/j.issn.0529-1356.2019.04.004

References

［1］ Kivimki M, Steptoe A. Effects of stress on the development and progression of cardiovascular disease ［J］. Nat Rev Cardiol, 2018, 15(4):215-229.

［2］ Hackett RA, Steptoe A. Type 2 diabetes mellitus and psychological stress-a modifiable risk factor ［J］. Nat Rev Endocrinol, 2017, 13(9):547-560.

［3］ Kloet ER De, Jo?ls M, Holsboer F. Stress and the brain: from adaptation to disease ［J］. Nat Rev Neurosci, 2005, 6（6）:463-475.

［4］ Rafacho A, Ortsater H, Nadal A, et al. Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes ［J］. J Endocrinol, 2014, 223(3): R49-R62.

［5］ Liang B, Zheng X, Xia WW, et al. Establishment of chronic constraint stress animal model and its application in the study of hyperglycemia ［J］. Journal of Sichuan University（Medical Science Edition）, 2013, 44(3): 470-475.（in Chinese）

梁冰, 郑翔, 夏卫维, 等. 慢性束缚应激造模及观测高血糖相关指标的方法探索［J］. 四川大学学报(医学版)，2013，44(3): 470-475.

［6］ Li XJ, Zhang W, Liang B, et al. Up-expression of GAD65 in the amygdala of the rat model of chronic immobilization stress with elevated blood glucose ［J］. Auton Neurosci, 2012, 166(1-2): 77-80.

［7］ Flak JN, Solomon MB, Jankord R, et al. Identification of chronic stress-activated regions reveals a potential recruited circuit in rat brain ［J］. Eur J Neurosci, 2012, 36(4): 2547-2555.

［8］ Oliveira SA, Chuffa LG, Fioruci-Fontanelli BA, et al. Apoptosis of purkinje and granular cells of the cerebellum following chronic ethanol intake ［J］. Cerebellum, 2014, 13(6): 728-738.

［9］ Wan RL, Pan Q, An XH, et al. Neural immune change in depression model mice ［J］. Acta Anatomica Sinica, 2018,49(3):281-287. (in Chinese)

万仁玲, 潘绮安晓虹,等. 抑郁症小鼠模型的神经免疫改变［J］.解剖学报, 2018, 49(3):281-287.

［10］ Menges S, Minakaki G, Schaefer PM, et al. Alpha-synuclein prevents the formation of spherical mitochondria and apoptosis under oxidative stress ［J］. Sci Rep, 2017, 7:42942.

[11］ Del Río P, Montiel T, Massieu L. Contribution of NMDA and non-NMDA receptors to in vivo glutamate-induced calpain activation in the rat striatum relation to neuronal damage ［J］. Neurochem Res, 2008, 33(8):1475-1483.

［12］ Wang YZ, Wang W, Li Z, et al. A novel perspective on neuron study: damaging and promoting effects in different neurons induced by mechanical stress ［J］. Biomech Model Mechanobiol, 2016, 15(5):1019-1027.

［13］ Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates ［M］. Third ed. Beijing: People’s Health Publishing House, 2005：1-76. (in Chinese)

Paxinos G, Watson C. 大鼠脑立体定位图谱［M］. 第3版.北京:人民卫生出版社, 2005：1-76.

［14］ Fulford AJ, Harbuz MS. An introduction to the HPA axis ［J］. Tech Behav Neural Sci, 2005, 15(5):143-165.

［15］ McEwen BS. Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators ［J］. Eur J Pharmacol, 2008, 583(2-3):174-185.

［16］ De Guia RM, Rose AJ, Herzig S. Glucocorticoid hormones and energy homeostasis ［J］. Horm Mol Biol Clin Invest, 2014, 19(2):117-128.

［17］ Zhang B, Zhang Y, Wu W, et al. Chronic glucocorticoid exposure activates BK-NLRP1 signal involving in hippocampal neuron damage ［J］. J Neuroinflammation, 2017, 14(1):139.

［18］ Fransson L, Franzén S, Rosengren Ⅴ, et al. β-cell adaptation in a mouse model of glucocorticoid-induced metabolic syndrome ［J］. J Endocrinol, 2013, 219(3):231-241.

［19］ Myers B, Scheimann JR, Franco-Villanueva A, et al. Ascending mechanisms of stress integration: implications for brainstem regulation of neuroendocrine and behavioral stress responses ［J］. Neurosci Biobehav Rev, 2017, 74(Pt B):366-375.

［20］ Himmi T, Perrin J, Dallaporta M, et al. Effects of lactate on glucose-sensing neurons in the solitary tract nucleus ［J］. Physiol Behav, 2001, 74(3):391-397.

［21］ McRitchie DA, Tork Ⅰ. The internal organization of the human solitary nucleus ［J］. Brain Res Bull, 1993, 31(12):171-193.

［22］ Ganchrow D, Ganchrow JR, Cicchini Ⅴ, et al. Nucleus of the solitary tract in the C57BL/6J mouse: subnuclear parcellation, chorda tympani nerve projections, and brainstem connections ［J］. J Comp Neurol, 2014, 522(7):1565-1596.

［23］ Chen LQ, Cheung LS, Feng L, et al. Transport of sugars ［J］. Annu Rev Biochem, 2015, 84:865-894.

［24］ Deem JD, Muta K, Scarlett JM, et al. How should we think about the role of the brain in glucose homeostasis and diabetes ［J］? Diabetes, 2017, 66(7):1758-1765.

［25］ Osundiji MA, Evans ML. Brain control of insulin and glucagon secretion ［J］. Endocrinol Metab Clin N Am, 2013, 42(1):1-14.

［26］ Herman JP. Regulation of hypothalamo-pituitary-adrenocortical responses to stressors by the nucleus of the solitary tract/dorsal vagal complex ［J］. Cell Mol Neurobiol, 2018, 38(1):25-35.

［27］ Sousa N. The dynamics of the stress neuromatrix ［J］. Mol Psychiatry, 2016, 21(3):302-312.

［28］ Kim JG, Jung HS, Kim KJ, et al. Basal blood corticosterone level is correlated with susceptibility to chronic restraint stress in mice ［J］. Neurosci Lett, 2013, 555:137-142.

［29］ Zhao HL, Alam A, San CY, et al. Molecular mechanisms of brain-derived neurotrophic factor in neuroprotection: recent developments ［J］. Brain Res, 2017, 1665:1-21.