Neurogenesis in Neurogenic Niches of the Brain in Experimental Alzheimer’s Disease at the Presymptomatic Stage of Neurodegeneration Development

• Published in: Cell and tissue biology 2023-12, Vol.17 (6), p.619-626
• Main Authors: Averchuk, A. S., Ryazanova, M. V., Rozanova, N. A., Kolotyeva, N. A., Stavrovskaya, A. V., Novikova, S. V., Salmina, A. B.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Apoptosis; Beta2 protein; Biomedical and Life Sciences; Cell Biology; Cognitive ability; Developmental stages; Hippocampus; Life Sciences; Nestin; Neurodegeneration; Neurodegenerative diseases; Neurogenesis; Pax6 protein; Progenitor cells; Sodium chloride; Subventricular zone; β-Amyloid
• ISSN: 1990-519X; 1990-5203
• DOI: 10.1134/S1990519X23060020

Deciphering the mechanisms of neurodegeneration development at the presymptomatic stage is an urgent task, the solution of which will help optimize the methods of early diagnostics and prevention of Alzheimer’s disease (AD). In this work, we studied the features of neurogenesis in the neurogenic niches of the brain in experimental AD at the presymptomatic stage of neurodegeneration. Modeling of AD in vivo was carried out in experimental animals (male mice, C57BL/6 at the age of 8 months). To do this, the control group (n = 30) was injected with 2 µL of a 0.9% NaCl solution in the CA1 field of the hippocampus, and the experimental group (n = 30) was injected with a 1M solution (2 µL bilaterally) of oligomerized β-amyloid 25–35 (Aβ25–35). Animal cognitive impairments were assessed using the passive avoidance conditioned reaction test (PACR). For immunohistochemical studies, frozen brain sections were used, in which changes in the expression of markers Nestin, Pax6, NeuroD1, and VEGFR2 were analyzed; cell apoptosis was assessed by the TUNEL protocol in the subgranular zone (SGZ) and subventricular zone (SVZ) of the hippocampus. We have found multidirectional changes in the expression of neurogenesis markers, neoangiogenesis, and the severity of apoptosis in the SGZ and SVZ in the period 9–17 days after intrahippocampal administration of Aβ25–35. On day 9 of Alzheimer’s type neurodegeneration development, the expression of Pax6 and VEGFR2 in the SGZ and Nestin in the SVZ was increased. Subsequent application of the PACR protocol with presentation of an aversive stimulus (day 10) or the corresponding context (days 11 and 17) led to dynamic changes in the expression of cell markers at different stages of neurogenesis. Thus, at the presymptomatic stage of the development of Alzheimer’s type neurodegeneration, the SGZ and SVZ zones show signs of aberrant neurogenesis associated with a disruption in the pool of stem and progenitor cells and suppression of the production of neuroblasts (immature neurons) in the period preceding the formation of cognitive dysfunction.