Research output: Contribution to journal › Article › peer-review
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. / Rudnitskaya, Ekaterina A.; Burnyasheva, Alena O.; Kozlova, Tatiana A. et al.
In: International Journal of Molecular Sciences, Vol. 23, No. 3, 1134, 01.02.2022.Research output: Contribution to journal › Article › peer-review
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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 -
ID: 35323581