TY - JOUR

T1 - Changes in Glial Support of the Hippocampus during the Development of an Alzheimer’s Disease‐like Pathology and Their Correction by Mitochondria‐Targeted Antioxidant SkQ1

AU - Rudnitskaya, Ekaterina A.

AU - Burnyasheva, Alena O.

AU - Kozlova, Tatiana A.

AU - Peunov, Daniil A.

AU - Kolosova, Nataliya G.

AU - Stefanova, Natalia A.

N1 - Funding Information: Funding: This research was funded by the Russian Science Foundation, grant number 19‐15‐00044. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/2/1

Y1 - 2022/2/1

N2 - Astrocytes and microglia are the first cells to react to neurodegeneration, e.g., in Alz-heimer’s disease (AD); however, the data on changes in glial support during the most common (sporadic) type of the disease are sparse. Using senescence‐accelerated OXYS rats, which simulate key characteristics of sporadic AD, and Wistar rats (parental normal strain, control), we investigated hippocampal neurogenesis and glial changes during AD‐like pathology. Using immuno-histochemistry, we showed that the early stage of the pathology is accompanied by a lower inten-sity of neurogenesis and decreased astrocyte density in the dentate gyrus. The progressive stage is concurrent with reactive astrogliosis and microglia activation, as confirmed by increased cell densities and by the acquisition of cell‐specific gene expression profiles, according to transcriptome sequencing data. Besides, here, we continued to analyze the anti‐AD effects of prolonged supple-mentation with mitochondria‐targeted antioxidant SkQ1. The antioxidant did not affect neuro-genesis, partly normalized the gene expression profile of astrocytes and microglia, and shifted the resting/activated microglia ratio toward a decrease in the activated‐cell density. In summary, both astrocytes and microglia are more vulnerable to AD‐associated neurodegeneration in the CA3 area than in other hippocampal areas; SkQ1 had an anti‐inflammatory effect and is a promising modal-ity for AD prevention and treatment.

AB - Astrocytes and microglia are the first cells to react to neurodegeneration, e.g., in Alz-heimer’s disease (AD); however, the data on changes in glial support during the most common (sporadic) type of the disease are sparse. Using senescence‐accelerated OXYS rats, which simulate key characteristics of sporadic AD, and Wistar rats (parental normal strain, control), we investigated hippocampal neurogenesis and glial changes during AD‐like pathology. Using immuno-histochemistry, we showed that the early stage of the pathology is accompanied by a lower inten-sity of neurogenesis and decreased astrocyte density in the dentate gyrus. The progressive stage is concurrent with reactive astrogliosis and microglia activation, as confirmed by increased cell densities and by the acquisition of cell‐specific gene expression profiles, according to transcriptome sequencing data. Besides, here, we continued to analyze the anti‐AD effects of prolonged supple-mentation with mitochondria‐targeted antioxidant SkQ1. The antioxidant did not affect neuro-genesis, partly normalized the gene expression profile of astrocytes and microglia, and shifted the resting/activated microglia ratio toward a decrease in the activated‐cell density. In summary, both astrocytes and microglia are more vulnerable to AD‐associated neurodegeneration in the CA3 area than in other hippocampal areas; SkQ1 had an anti‐inflammatory effect and is a promising modal-ity for AD prevention and treatment.

KW - Alzheimer’s disease

KW - Astrocyte

KW - Microglia

KW - Mitochondria‐targeted antioxidant

KW - OXYS rats

KW - SkQ1

KW - Plastoquinone/administration & dosage

KW - Dentate Gyrus/chemistry

KW - Rats, Wistar

KW - Rats

KW - Male

KW - Gene Expression Profiling

KW - Alzheimer Disease/diet therapy

KW - Animals

KW - Mitochondria/drug effects

KW - Astrocytes/chemistry

KW - Dietary Supplements

KW - Gene Expression Regulation/drug effects

KW - Disease Models, Animal

UR - http://www.scopus.com/inward/record.url?scp=85122949376&partnerID=8YFLogxK

U2 - 10.3390/ijms23031134

DO - 10.3390/ijms23031134

M3 - Article

C2 - 35163053

AN - SCOPUS:85122949376

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 3

M1 - 1134

ER -