Evaluation of angiogenesis and microvascular remodeling in the subventricular zone of the brain of mice with experimental Alzheimer’s disease

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Abstract

BACKGROUND: Under the influence of external factors (learning), processes of microvasculature remodeling occur in the neurogenic niche to meet the metabolic needs of activated cells. However, it remains unclear how these mechanisms of brain plasticity are disrupted during neurodegeneration.

AIM: To study the expression features of markers of angiogenesis and microvascular remodeling in the subventricular zone of the brain during training of animals, including against the background of the development of Alzheimer’s-type neurodegeneration in them.

MATERIAL AND METHODS: The studies were carried out on C57BL/6 mice at the age of 8 months. Modeling of Alzheimer’s disease was carried out by intrahippocampal injection of 2 μl of a 1 mM solution of β-amyloid Aβ25-35. To assess cognitive deficits, a conditioned passive avoidance test using an aversive stimulus was used. The expression of LC3B, ZO1, VEGFR2, VEGFR3, CD146, ICAM2, Dll4, Tie2 in the subventricular zone per 100 DAPI-positive cells was assessed. The test results were processed using one-way ANOVA and Fisher's test, the Mann–Whitney U test, the results were considered significant at p <0.05.

RESULTS: On the 9th day after the administration of β-amyloid, before the application of the aversive stimulus, an increase in the expression level of LC3 (7.95±5.83%, p=0.045), CD146 (18.35±0.01%, p=0.045) was recorded, as well as VEGFR3 (17.13±5.05%, p=0.045), which continued to increase after the presentation of the stimulus (26.61±0.01%, p=0.045). By the beginning of registration of cognitive impairment (38th day of the experiment), the expression level of VEGFR2 (20.61±2.8%, p=0.045) and ICAM2 (126.61±41.28%, p=0.045) increased, the content of Dll4 (29.66±8.72%, p=0.045) and Tie2 (36.39±7.8%, p=0.045) decreased in animals with experimental Alzheimer’s disease.

CONCLUSION: An aversive stimulus stimulates microvascular remodeling mechanisms in the subventricular zone of the animal’s brain, but when exposed to β-amyloid, these processes are significantly disrupted.

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About the authors

Anton S. Averchuk

Research Center of Neurology

Author for correspondence.
Email: antonaverchuk@yandex.ru
ORCID iD: 0000-0002-1284-6711
SPIN-code: 7276-8713
Scopus Author ID: 57204197597
ResearcherId: I-1075-2018

Cand. Sci. (Biol.), Assoc. Prof., Researcher, Laboratory of Neurobiology and Tissue Engineering, Brain Science Institute

Russian Federation, Moscow

Maria V. Ryazanova

Research Center of Neurology

Email: mashenka.ryazanova@list.ru
ORCID iD: 0000-0003-0700-4912

Postgrad. Stud., Laboratory of Neurobiology and Tissue Engineering, Brain Science Institute

Russian Federation, Moscow

Alla V. Stavrovskaya

Research Center of Neurology

Email: alla_stav@mail.ru
ORCID iD: 0000-0002-8689-0934

Cand. Sci. (Biol.), Head, Laboratory of Experimental Pathology of the Nervous System, Brain Science Institute

Russian Federation, Moscow

Svetlana V. Novikova

Research Center of Neurology

Email: levik_82@mail.ru
ORCID iD: 0009-0008-3905-1928

Junior Researcher, Laboratory of Experimental Pathology of the Nervous System, Brain Science Institute

Russian Federation, Moscow

Alla B. Salmina

Research Center of Neurology

Email: allasalmina@mail.ru
ORCID iD: 0000-0003-4012-6348

M.D., D. Sci. (Med), Prof., Chief Researcher, Head, Laboratory of Experimental Pathology of the Nervous System, Brain Science Institute

Russian Federation, Moscow

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Changes in the expression level of LC3 (A) in endothelial cells (ZO1-immunopositive cells) and CD146 (B) in the brain subventricular zone of animals in the control group and in experimental Alzheimer's disease (AD) to 9th (dark columns) and 38th (light columns) days

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3. Fig. 2. VEGFR2 (А) and VEGFR3 (Б) in the brain subventricular zone of animals in the control group and in experimental Alzheimer's disease on the 9th (dark columns) and 38th (light columns) days

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4. Fig. 3. Changes in the expression level of ICAM2, Dll4, Tie2 in the brain subventricular zone of animals in the control group and in experimental Alzheimer's disease on the 9th (dark columns) and 38th (light columns) days

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5. Fig. 4. Changes in the number of ICAM2-immunopositive cells in the brain subventricular zone of mice in control (A) and with experimental Alzheimer's disease on the 9th day of the experiment (B). Arrows indicate ICAM2-immunopositive cells; nuclei are stained with DAPI

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