The role of vascular injury within the conditions of choline deficiency in rats with scopolamine-induced alzheimer's type dementia

Authors

DOI:

https://doi.org/10.26641/1997-9665.2021.3.66-75

Keywords:

Alzheimer's disease, blood vessels, brain, scopolamine butylbromide, rats

Abstract

Background. The relationship between choline deficiency and vascular dysfunction continues to be relevant in the study of Alzheimer's disease. Objective. To study the morphological characteristics of vascular injury within the conditions of choline deficiency in rats with scopolamine-induced Alzheimer's type dementia. Methods. The experiment was performed on 48 WAG population male rats weighing 180-230 gr. Rats from groups Scop-14, Scop-14-SC, Scop-28, Scop-28-SC were injected intraperitoneally with scopolamine (Scop) butylbromide at a dosage of 1 mg/kg of body mass during 14 and 28 days and intravenously with mesenchymal stem cells (SC) at a single dosage of 500000 cells per 1 rat. Control animals (gr.C) were injected with 0.9% sodium chloride. Brain slides were stained with Congo-red and gallocyanine-chromium alum according to Einarson's method for total nucleic acids. The VEGF, E-cadherin expression was immunohistochemically determined in the brain cells cytoplasm. Results. The congophilic staining of the arteries walls, a decrease in endothelial cells with low the E-cadherin expression and an increase in the number of pericytes in the capillary wall was observed in the experimental groups. In gr.Scop-28 VEGF expression in endothelial cells, hippocampal neurons was greater than in gr.Scop-14. It indicated more intensive activation of angiogenesis and acetylcholine synthesis with correspondingly more pronounced vascular damage and choline deficiency. The cytoplasm of cortical neurons was diffusely labeled with VEGF antibodies in response to hypoxia, but the level of expression was almost no different from that in gr.C. In all groups, the optical density of the neuropile of the large hemispheres according to Einarson’s staining was reduced, i.e., the level of RNA in the neuronal processes was reduced. The introduction of stem cells restored the capillary wall due to young endothelial cells, reduced the VEFG synthesis in all studied cells and increased the RNA content in neuronal processes. Conclusion. The relationship between choline deficiency, neuronal process loss and vascular damage has been found. The blood vessels self-repair was occurred by substitution, after the stem cells introduction - by restitution.

References

  1. Verclytte S, Lopes R, Lenfant P, Rollin A, Semah F, Leclerc X, Pasquier F, Delmaire C. Cerebral Hypoperfusion and Hypometabolism Detected by Arterial Spin Labeling MRI and FDG-PET in Early-Onset Alzheimer's Disease. J Neuroimaging. 2016;26(2):207-212. DOI: 10.1111/jon.12264. Epub 2015 May 29. PMID: 26031943.
  2. Pluta R, Jabłoński M, Ułamek-Kozioł M, Kocki J, Brzozowska J, Januszewski S, Furmaga-Jabłońska W, Bogucka-Kocka A, Maciejewski R, Czuczwar SJ. Sporadic Alzheimer's disease begins as episodes of brain ischemia and ischemically dysregulated Alzheimer's disease genes. Mol Neurobiol. 2013;48(3):500-515. DOI: 10.1007/s12035-013-8439-1. Epub 2013 Mar 22. PMID: 23519520; PMCID: PMC3825141
  3. Montagne A, Zhao Z, Zlokovic BV. Alzheimer's disease: A matter of blood-brain barrier dysfunction? J Exp Med. 2017;214(11):3151-3169. DOI: 10.1084/jem.20171406. Epub 2017 Oct 23. PMID: 29061693; PMCID: PMC5679168.
  4. Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012;4(147):147ra111. DOI: 10.1126/scitranslmed.3003748. PMID: 22896675; PMCID: PMC3551275.
  5. Aldea R, Weller RO, Wilcock DM, Carare RO, Richardson G. Cerebrovascular Smooth Muscle Cells as the Drivers of Intramural Periarterial Drainage of the Brain. Front Aging Neurosci. 2019;11:1. DOI: 10.3389/fnagi.2019.00001. PMID: 30740048; PMCID: PMC6357927.
  6. Lecrux C, Sandoe CH, Neupane S, Kropf P, Toussay X, Tong XK, Lacalle-Aurioles M, Shmuel A, Hamel E. Impact of Altered Cholinergic Tones on the Neurovascular Coupling Response to Whisker Stimulation. J Neurosci. 2017;37(6):1518-1531. DOI: 10.1523/JNEUROSCI.1784-16.2016. Epub 2017 Jan 9. PMID: 28069927; PMCID: PMC6705676.
  7. Lim SA, Kang UJ, McGehee DS. Striatal cholinergic interneuron regulation and circuit effects. Front Synaptic Neurosci. 2014;6:22. DOI: 10.3389/fnsyn.2014.00022. PMID: 25374536; PMCID: PMC4204445.
  8. Austin SA, Katusic ZS. Partial loss of endothelial nitric oxide leads to increased cerebrovascular beta amyloid. J Cereb Blood Flow Metab. 2020;40(2):392-403. DOI: 10.1177/0271678X18822474. Epub 2019 Jan 7. PMID: 30614363; PMCID: PMC7370614.
  9. Nizari S, Wells JA, Carare RO, Romero IA, Hawkes CA. Loss of cholinergic innervation differentially affects eNOS-mediated blood flow, drainage of Aβ and cerebral amyloid angiopathy in the cortex and hippocampus of adult mice. Acta Neuropathol Commun. 2021;9(1):12. DOI: 10.1186/s40478-020-01108-z. PMID: 33413694; PMCID: PMC7791879.
  10. Deiko RD, Shtrygol' SY, Laryanovskaya YB, Gorbach TV, Gubina-Vakulik GI, Devyatkina NM, Shtrygol' DV. [Chronic blockade of central muscarinic receptors in rats induces primary pathogenetic links of alzheimer's disease]. Actual Problems of the Modern Medicine: Bulletin of Ukrainian Medical Stomatological Academy. 2017;17,3(59):13-25. Ukrainian.
  11. Lee H, Son HJ, Rhee PL, Kim JJ, Rhee JC. Unexpected anterograde amnesia associated with Buscopan used as a predmedication for endocscopy. World J Gastroenterol. 2007;13(28):3895-3896. DOI: 10.3748/wjg.v13.i28.3895. PMID: 17657850; PMCID: PMC4611228.
  12. Zorenko YM, Pavlova OO, Gorbach TV, Martynova SM. [Role of hypoxia and mitochondrial dysfunction in the mechanism of the experimental alzheimer’s type dementia induced by different ways in rats and assessment of possibilities to correct this condition by using mesenchymal stem cells]. Bulletin of Problems Biology and Medicine. Clinical and Experimental Medicine. 2021;1(159):66-72.
  13. Pyatikop V, Msallam M, Shchegelskaya E, Kutovoy I, Gubina-Vakulik G. Migration features of labeled bone marrow mesenchymal stem cells in rats with modeled Parkinson-like syndrome. Ukrainian Neurosurgical Journal. 2014;3:42-48. Ukrainian. DOI 10.29254/2077-4214-2021-1-159-66-72.
  14. Romaniuk A, Gyryavenko N, Lyndin M, Piddubnyi A, Sikora V, Korobchanska A. Primary cancer of the fallopian tubes: histological and immunohistochemical features. Folia medica Cracoviensia. 2016;4:71-80.
  15. Kaporskij LN, Prohorov AM, Alekseev DM, Baldin AM. [Optical density. Physical encyclopedia]. Moscow: Great Russian Encyclopedia; 1992. 672 p. Russian.
  16. Hernández-Rodríguez M, Arciniega-Martínez IM, García-Marín ID, Correa-Basurto J, Rosales-Hernández MC. Chronic Administration of Scopolamine Increased GSK3βP9, Beta Secretase, Amyloid Beta, and Oxidative Stress in the Hippocampus of Wistar Rats. Mol Neurobiol. 2020;57(9):3979-3988. DOI: 10.1007/s12035-020-02009-x. Epub 2020 Jul 7. PMID: 32638218.
  17. Gorbach T, Nakonechna O, Tkachenko A, Shcholok T, Onikova A. Levels of thyroid hormones and indices of energy metabolism in the cerebral cortex of rats with experimental Alzheimer’s disease. Neurophysiology. 2018;50(3):159–165. https://doi.org/10.1007/s11062-018-9732-4
  18. Garcia KO, Ornellas FL, Martin PK, Patti CL, Mello LE, Frussa-Filho R, Han SW, Longo BM. Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's disease. Front Aging Neurosci. 2014;6:30. DOI: 10.3389/fnagi.2014.00030. PMID: 24639647; PMCID: PMC3945612.
  19. Acosta L, Morcuende S, Silva-Hucha S, Pastor AM, de la Cruz RR. Vascular Endothelial Growth Factor (VEGF) Prevents the Downregulation of the Cholinergic Phenotype in Axotomized Motoneurons of the Adult Rat. Front Mol Neurosci. 2018;11:241. DOI: 10.3389/fnmol.2018.00241. PMID: 30050409; PMCID: PMC6052088.
  20. Kimura K, Matsumoto K, Ohtake H, Oka JI, Fujiwara H. Endogenous acetylcholine regulates neuronal and astrocytic vascular endothelial growth factor expression levels via different acetylcholine receptor mechanisms. Neurochemistry International. 2018;118:42-51. DOI: 10.1016/j.neuint.2018.04.012. PMID: 29705288.
  21. Haam J, Yakel JL. Cholinergic modulation of the hippocampal region and memory function. J Neurochem. 2017;142(2):111-121. DOI: 10.1111/jnc.14052. PMID: 28791706; PMCID: PMC5645066.
  22. Pilling D, Gomer RH. The Development of Serum Amyloid P as a Possible Therapeutic. Front. Immunol. 2018;9:2328. DOI: 10.3389/fimmu.2018.02328
  23. Tkachenko AS, Gubina-Vakulyck GI, Polikarpova HV, Onishchenko AI. [Effect of the food additive E407a on E-cadherin expression in the small intestine]. Health and Ecology Issues. 2021;(2):94-101. Russian. https://doi.org/10.51523/2708-6011.2021-18-2-14
  24. Naaldijk Y, Jäger C, Fabian C, Leovsky C, Blüher A, Rudolph L, Hinze A, Stolzing A. Effect of systemic transplantation of bone marrow-derived mesenchymal stem cells on neuropathology markers in APP/PS1 Alzheimer mice. Neuropathol Appl Neurobiol. 2017;43(4):299-314. DOI: 10.1111/nan.12319. Epub 2016 Apr 19. PMID: 26918424.
  25. Jalali F, Afshari R, Babaei A. Smoking crushed hyoscine/scopolamine tablets as drug abuse. Subst Use Misuse. 2014;49(7):793-797. DOI: 10.3109/10826084.2014.880178. Epub 2014 Feb 4. PMID: 24494624.
  26. Strano-Rossi S, Mestria S, Bolino G, Polacco M, Grassi S, Oliva A. Scopolamine fatal outcome in an inmate after buscopan® smoking. Int J Legal Med. 2021;135(4):1455-1460. DOI: 10.1007/s00414-021-02583-2. Epub 2021 Apr 23. PMID: 33890166; PMCID: PMC8062144.
  27. Mityanand Ramnarine MD. Anticholinergic toxicity [Internet]. Practice Essentials, Pathophysiology, Epidemiology. Medscape; 2020 [cited 2021 Sept 7]. Available from: https://emedicine.medscape.com/article/812644-overview
  28. Zorenko Y, Pavlova O, Shchegelskaya E, Omelchenko E, Gorbach T, Vasylyeva I. Mesenchymal Stem Cells Ameliorate Scopolamine Induced Dementia Of Alzheimer’s Type. Teikyo Medical Journal. 2021;44(3):793-805.

Published

2021-12-25

How to Cite

The role of vascular injury within the conditions of choline deficiency in rats with scopolamine-induced alzheimer’s type dementia. (2021). Морфологія / Morphologia / Morfologìâ, 15(3), 66–75. https://doi.org/10.26641/1997-9665.2021.3.66-75

Issue

Section

Статті