Peralta, F. | Search bioRxiv

bioRxiv2026

Understanding Brain Aging Through Behavioural and Microglial Changes: A Lifespan Approach

Aging is characterized by progressive physiological decline linked to inflammaging, a chronic low-grade inflammatory state. This study investigates age-related behavioural changes and their correlation with microglial function in female Sprague Dawley rats across their lifespan. Using a longitudinal design at 2, 6, 12, and 24 months of age, we assessed motor performance, mood-related behaviours, and spatial cognition alongside microglial morphometric analysis in key brain regions. Results showed that motor and cognitive performance began to decline significantly at 12 months, with severe impairments and depressive-like behaviours appearing by 24 months. These deficits were paralleled by progressive gliosis in the hippocampus and striatum. Microglial morphometric analysis further indicated a more reactive, region-dependent phenotype, with cells in the striatum adopting a smaller area, reduced perimeter, and fewer intersections. These findings provide compelling evidence for significant age-dependent deterioration in motor performance, mood regulation, and cognitive abilities in female rats. Our data strongly suggest an underlying progression of neurobiological changes, with microglial dysfunction and neuroinflammation being central candidates. This research contributes valuable insights into the cellular correlates of behavioural decline across the female lifespan, serving as a reference for the multifaceted changes that occur during normal aging.

neuroscience↗

bioRxiv2024

The integration of tandem gene repeats via a bacterial type-II toxin-antitoxin-mediated gene amplification (ToxAmp) system and stability visualisation in Saccharomyces cerevisiae

Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms, like human diseases and microbial productivities of target bioproducts. Here, we develop a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualise the evolutionary trajectories of gene repeats. We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification (ToxAmp) modules, and accidentally re-visited the high-level capacity of multi-fragment co-transformation in S. cerevisiae. This system delivered the multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection. Inducing the toxin (RelE) expressing via a copper (II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin (RelB) module, resulting in [~]40 copies of a green fluorescence reporter (GFP) gene per copy of genome. The copy-number changes, increasing and decreasing, and stable maintenance were visualised using the GFP and blue chromoprotein AeBlue as reporters. Copy-number increasing happened spontaneously not depending on a selection pressure and was quickly enriched through toxin-antitoxin-mediated selection. In summary, the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications. Table of Contents Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/578080v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@75d1f3org.highwire.dtl.DTLVardef@12aafeforg.highwire.dtl.DTLVardef@184a1a5org.highwire.dtl.DTLVardef@90586a_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗