open access

Ahead of Print
Original article
Submitted: 2023-01-09
Accepted: 2023-09-11
Published online: 2023-09-29
Get Citation

Analysis of age-related differences in hypoxia-related factors in yak brain tissue

Lan Zhang1, Kun Yang1234, Xiao Tan1, Yazhu Cai, Haie Ding1, Rui Li1234, Yiyang Zhang1234, Manlin Zhou1234, Zuli Ben1, Qian Zhang5, Zilin Qiao1234
·
Pubmed: 37822067
Affiliations
  1. College of Life Science and Engineering, Northwest Minzu University, Lan Zhou, Gansu, China
  2. Gansu Tech Innovation Centre of Animal Cell, Biomedical Research Center, Northwest Minzu University, Lan Zhou, Gansu, China
  3. Engineering Research Centre of Key Technology and Industrialization of Cell-based Vaccine, Ministry of Education, Lan Zhou, Gansu, China
  4. Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Centre, Northwest Minzu University, Lan Zhou, Gansu, China
  5. College of Veterinary Medicine, Gansu Agricultural University, Lan Zhou, Gansu Province, China

open access

Ahead of Print
ORIGINAL ARTICLES
Submitted: 2023-01-09
Accepted: 2023-09-11
Published online: 2023-09-29

Abstract

The brain is an important part of the mammalian nervous system, is highly sensitive to hypoxia, and plays an important role in the adaptation of the body to hypoxic environments. This study was conducted to study the distribution and expression of hypoxia-related factors (hypoxia-inducible factor 1α, HIF-1α; erythropoietin, EPO; vascular endothelial growth factor, VEGF; vascular cell adhesion molecule, VCAM) in the cerebellum, cerebrum, medulla oblongata, and corpora quadrigemina in yaks of different ages (4d, 6-months-old and adult). Paraffin sections were obtained from the cerebellum, cerebrum, medulla oblongata, and corpora quadrigemina of healthy yak for 4-day-old, 6-months-old and adult yaks. Histological characteristics were assessed by haematoxylin staining. Immunohistochemical staining was performed to detect the distribution and expression of HIF-1α, EPO, VEGF and VCAM proteins. Immunohistochemical results showed that HIF-1α, EPO, VEGF, and VCAM were expressed in the pyramidal cell layer of the yak cerebrum, and distributed in the cerebellum granulose cell layer, Purkinje cell layer and medulla layer, and were mainly positive in Purkinje cells and medulla. It is expressed in the cell bodies of the medulla oblongata and the quadrimatous neurons. The expression level in the medulla oblongata was higher, indicating may play a crucial role in functional cohesion. The expression of HIF-1α in 4 d cerebellar tissues was higher than that in other age groups, and the expression of HIF-1α in the medulla oblongata increased with age. In addition, the expression levels of EPO and VEGF in the 6-month-old group were slightly higher than those in the other age groups. It is speculated that EPO and VEGF have obvious protective effects on brain tissue in the 6-month-old age group; VCAM showed no significant differences in the cerebrum, cerebellum, medulla oblongata, or corpora quadrigemina of the yaks. This study provides basic data for further exploration of the adaptive mechanism of plateau yak brain tissue.

Abstract

The brain is an important part of the mammalian nervous system, is highly sensitive to hypoxia, and plays an important role in the adaptation of the body to hypoxic environments. This study was conducted to study the distribution and expression of hypoxia-related factors (hypoxia-inducible factor 1α, HIF-1α; erythropoietin, EPO; vascular endothelial growth factor, VEGF; vascular cell adhesion molecule, VCAM) in the cerebellum, cerebrum, medulla oblongata, and corpora quadrigemina in yaks of different ages (4d, 6-months-old and adult). Paraffin sections were obtained from the cerebellum, cerebrum, medulla oblongata, and corpora quadrigemina of healthy yak for 4-day-old, 6-months-old and adult yaks. Histological characteristics were assessed by haematoxylin staining. Immunohistochemical staining was performed to detect the distribution and expression of HIF-1α, EPO, VEGF and VCAM proteins. Immunohistochemical results showed that HIF-1α, EPO, VEGF, and VCAM were expressed in the pyramidal cell layer of the yak cerebrum, and distributed in the cerebellum granulose cell layer, Purkinje cell layer and medulla layer, and were mainly positive in Purkinje cells and medulla. It is expressed in the cell bodies of the medulla oblongata and the quadrimatous neurons. The expression level in the medulla oblongata was higher, indicating may play a crucial role in functional cohesion. The expression of HIF-1α in 4 d cerebellar tissues was higher than that in other age groups, and the expression of HIF-1α in the medulla oblongata increased with age. In addition, the expression levels of EPO and VEGF in the 6-month-old group were slightly higher than those in the other age groups. It is speculated that EPO and VEGF have obvious protective effects on brain tissue in the 6-month-old age group; VCAM showed no significant differences in the cerebrum, cerebellum, medulla oblongata, or corpora quadrigemina of the yaks. This study provides basic data for further exploration of the adaptive mechanism of plateau yak brain tissue.

Get Citation

Keywords

Yaks, brain tissue, development, EPO, VEGF, VCAM

About this article
Title

Analysis of age-related differences in hypoxia-related factors in yak brain tissue

Journal

Folia Morphologica

Issue

Ahead of Print

Article type

Original article

Published online

2023-09-29

Page views

188

Article views/downloads

171

DOI

10.5603/fm.93596

Pubmed

37822067

Keywords

Yaks
brain tissue
development
EPO
VEGF
VCAM

Authors

Lan Zhang
Kun Yang
Xiao Tan
Yazhu Cai
Haie Ding
Rui Li
Yiyang Zhang
Manlin Zhou
Zuli Ben
Qian Zhang
Zilin Qiao

References (30)
  1. Anderson GK, Rosenberg AJ, Barnes HJ, et al. Peaks and valleys: oscillatory cerebral blood flow at high altitude protects cerebral tissue oxygenation. Physiol Meas. 2021; 42(6).
  2. Arcasoy MO. Non-erythroid effects of erythropoietin. Haematologica. 2010; 95(11): 1803–1805.
  3. Chen GH, Li XL, Deng YQ, et al. The Molecular Mechanism of EPO Regulates the Angiogenesis after Cerebral Ischemia through AMPK-KLF2 Signaling Pathway. Crit Rev Eukaryot Gene Expr. 2019; 29(2): 105–112.
  4. Chong ZZ, Kang JQ, Maiese K. Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cysteine proteases. Circulation. 2002; 106(23): 2973–2979.
  5. Ding Y, Zhang Na, Li J, et al. Molecular cloning and expression of ghrelin in the hypothalamus-pituitary-gastrointestinal tract axis of the Yak (Bos grunniens) in the Qinghai-Tibetan Plateau. Anat Histol Embryol. 2018; 47(6): 583–590.
  6. Ding YP, Yu HS, Wang JL, et al. Immunoexpression of aquaporins 1, 2, 3 and 4 in kidney of yak (Bos grunniens) on the Qinghai-Tibetan Plateau. Biotech Histochem. 2019; 94(1): 48–52.
  7. Fan X, Heijnen CJ, van der Kooij MA, et al. The role and regulation of hypoxia-inducible factor-1alpha expression in brain development and neonatal hypoxic-ischemic brain injury. Brain Res Rev. 2009; 62(1): 99–108.
  8. Feng J, Wang W. Hypoxia pretreatment and EPO-modification enhance the protective effects of MSC on neuron-like PC12 cells in a similar way. Biochem Biophys Res Commun. 2017; 482(2): 232–238.
  9. He Y, Yu S, Hu J, et al. Changes in the anatomic and microscopic structure and the expression of HIF-1α and VEGF of the yak heart with aging and hypoxia. PLoS One. 2016; 11(2): e0149947.
  10. Kato S, Aoyama M, Kakita H, et al. Endogenous erythropoietin from astrocyte protects the oligodendrocyte precursor cell against hypoxic and reoxygenation injury. J Neurosci Res. 2011; 89(10): 1566–1574.
  11. Li Xu, Chen Y, Shao S, et al. Oxidative stress induces the decline of brain EPO expression in aging rats. Exp Gerontol. 2016; 83: 89–93.
  12. Ma J, Wang C, Sun Y, et al. Comparative study of oral and intranasal puerarin for prevention of brain injury induced by acute high-altitude hypoxia. Int J Pharm. 2020; 591: 120002.
  13. Miyamoto Y, Torii T, Tanoue A, et al. VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination. Nat Commun. 2016; 7: 13478.
  14. Moreau N, Mauborgne A, Couraud PO, et al. Could an endoneurial endothelial crosstalk between Wnt/β-catenin and Sonic Hedgehog pathways underlie the early disruption of the infra-orbital blood-nerve barrier following chronic constriction injury? Mol Pain. 2017; 13: 1744806917727625.
  15. Ogunshola OO, Bogdanova AYu. Epo and non-hematopoietic cells: what do we know? Methods Mol Biol. 2013; 982: 13–41.
  16. Ott C, Martens H, Hassouna I, et al. Widespread expression of erythropoietin receptor in brain and its induction by injury. Mol Med. 2015; 21(1): 803–815.
  17. Pagel H, Engel A, Jelkmann W. Erythropoietin induction by hypoxia. A comparison of in vitro and in vivo experiments. Adv Exp Med Biol. 1992; 317: 515–519.
  18. Ren Q, Jiang ZH, Zhang XF, et al. Effects of erythropoietin on neonatal hypoxia-ischemia brain injury in rat model. Physiol Behav. 2017; 169: 74–81.
  19. Riksen NP, Hausenloy DJ, Yellon DM. Erythropoietin: ready for prime-time cardioprotection. Trends Pharmacol Sci. 2008; 29(5): 258–267.
  20. Sakanaka M, Wen TC, Matsuda S, et al. In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci U S A. 1998; 95(8): 4635–4640.
  21. Sanchez PE, Fares RP, Risso JJ, et al. Optimal neuroprotection by erythropoietin requires elevated expression of its receptor in neurons. Proc Natl Acad Sci U S A. 2009; 106(24): 9848–9853.
  22. Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol. 1992; 12(12): 5447–5454.
  23. Sirén AL, Knerlich F, Poser W, et al. Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain. Acta Neuropathol. 2001; 101(3): 271–276.
  24. Sköld M, Cullheim S, Hammarberg H, et al. Induction of VEGF and VEGF receptors in the spinal cord after mechanical spinal injury and prostaglandin administration. Eur J Neurosci. 2000; 12(10): 3675–3686.
  25. Sun L. F-box and WD repeat domain-containing 7 (FBXW7) mediates the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway to affect hypoxic-ischemic brain damage in neonatal rats. Bioengineered. 2022; 13(1): 560–572.
  26. Wakhloo D, Scharkowski F, Curto Y, et al. Functional hypoxia drives neuroplasticity and neurogenesis via brain erythropoietin. Nat Commun. 2020; 11(1): 1313.
  27. Wenger RH. Mammalian oxygen sensing, signalling and gene regulation. J Exp Biol. 2000; 203(8): 1253–1263.
  28. Wittko-Schneider IM, Schneider FT, Plate KH. Brain homeostasis: VEGF receptor 1 and 2-two unequal brothers in mind. Cell Mol Life Sci. 2013; 70(10): 1705–1725.
  29. Zhang J, Feng L, Hou C, et al. Health benefits on cardiocerebrovascular disease of reducing exposure to ambient fine particulate matter in Tianjin, China. Environ Sci Pollut Res Int. 2020; 27(12): 13261–13275.
  30. Zhou J, Yu S, He J, et al. Segmentation features and structural organization of the intrapulmonary artery of the yak. Anat Rec (Hoboken). 2013; 296(11): 1775–1788.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., Grupa Via Medica, Świętokrzyska 73, 80–180 Gdańsk, Poland

tel.: +48 58 320 94 94, faks: +48 58 320 94 60, e-mail: viamedica@viamedica.pl