PhD Scientific Days 2023

Neurosciences - Posters H

Age-related Changes of Microglia in Wistar Rats

Text of the abstract

Alzheimer’s disease (AD) is one of the most prevalent types of neurodegenerative diseases leading to dementia. There is still no consensus concerning the initial mechanisms of AD pathogenesis. The impact of inflammaging, or chronic age-related low-grade systemic inflammation, is one of the most perspective hypotheses so far. According to recent data microglia, which are resident immune cells in the CNS, might play the key role of AD development as well, and these cells also undergo the processes of cellular senescence.
The purpose of this work was to study morphofunctional changes of microglia in adult and old Wistar rats to reveal age-related alterations.
The work was performed on adult (n=10, age 3 months) and old (n=10, age 24 months) male Wistar rats. For ICH-P study, frontal histological sections of brains were stained with rabbit antibodies Iba1 and secondary HRP Donkey-anti-Rabbit antibodies. The expression of Il-6, Tnf-α, Il-10, Tgf-β, iNos, and Mmp9 mRNA was assayed by real-time qPCR in tissue fragments of the prefrontal cortex. The results were analyzed by Statistica 8.0 software (StatSoft, Inc.) using Mann-Whitney U-Test.
In a morphological study, adult rats’ microglia had a regular size and thin ramified processes, which are features of resting functional state. At the same time, old rats’ microglia had an increased size and spheroidal swelling, hypertrophic, beaded, and tortuous processes. The result of qPCR showed that Il-6 and Tnf-α expression levels were higher in old rats than in adult rats by 1.5-fold and 3-fold accordingly. Also iNos, which is a marker of M1 activated microglia, was 5-fold in old rats in comparison with adult rats. Old rats group showed no Il-10 expression at all, whereas the expression level of Tgf-β was 7.25-fold higher in adult rats. At the same time Mmp9, which is a marker of M2 activated microglia, was also 3-fold in old rats group.
Hence, obtained data demonstrate morphological changes of microglial cells, the decreasing of anti-inflammatory cytokines expression levels and the increasing of pro-inflammatory ones as well as microglia activation markers in old rats. This study confirms a great deal of differences between adult and old rodents’ physiological state. Since old rats demonstrate age-related changes similar to humans’, using aged animals for modeling of neurodegeneration is supposed to be more relevant.
Number of state registration of research, development, and technological work for civil purposes—122030200530-6