Analysis of age-related differences in hypoxia-related factors in 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 analyse 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.
Keywords: Yaksbrain tissuedevelopmentEPOVEGFVCAM
References
- 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).
- Arcasoy MO. Non-erythroid effects of erythropoietin. Haematologica. 2010; 95(11): 1803–1805.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Ogunshola OO, Bogdanova AYu. Epo and non-hematopoietic cells: what do we know? Methods Mol Biol. 2013; 982: 13–41.
- 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.
- 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.
- 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.
- Riksen NP, Hausenloy DJ, Yellon DM. Erythropoietin: ready for prime-time cardioprotection. Trends Pharmacol Sci. 2008; 29(5): 258–267.
- 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.
- 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.
- 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.
- Sirén AL, Knerlich F, Poser W, et al. Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain. Acta Neuropathol. 2001; 101(3): 271–276.
- 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.
- 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.
- Wakhloo D, Scharkowski F, Curto Y, et al. Functional hypoxia drives neuroplasticity and neurogenesis via brain erythropoietin. Nat Commun. 2020; 11(1): 1313.
- Wenger RH. Mammalian oxygen sensing, signalling and gene regulation. J Exp Biol. 2000; 203(8): 1253–1263.
- 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.
- 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.
- 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.
