Biology subjects

Numa, C.

Publications and source records attributed to Numa, C..

3 recordsLinked to original sources

bioRxiv2026

Synaptic mitochondrial oxidative stress drives individual variability in age-related cognitive decline in mice

Aging leads to cognitive decline with considerable individual variability, yet the biological mechanisms remain unclear. Here we performed ultrastructural and proteomic analyses of the medial prefrontal cortex (mPFC) alongside behavioral assessments of attentional set shifting in mice across age groups. Although reduced synaptic density did not consistently lead to cognitive decline, proteomic analyses of synaptosomes and whole tissue revealed that the molecular signatures associated with individual variability in cognitive decline were distinct from those associated with chronological aging, and that synaptic mitochondria and their proteins were more abundant in aged mice with greater cognitive decline. Moreover, treatment with the mitochondria-targeted antioxidant MitoQ reduced the abundance of synaptic mitochondrial proteins, including pro-apoptotic proteins, and mitigated age-related cognitive decline. These findings demonstrate that synaptic mitochondrial oxidative stress in the mPFC, distinct from chronological age-related processes, contributes to individual variability in age-related cognitive decline and offers a potential target for prevention and intervention.

animal behavior and cognition↗

bioRxiv2026

Aging Converts Microglial Repopulation into Maladaptive Reprogramming that Exacerbates Cognitive Deficits

Background and PurposeAging has been associated with neuroinflammation and cognitive decline. Microglial repopulation after pharmacological depletion has been proposed as a strategy to alleviate microglia-driven neuropathology. However, the effects of microglial repopulation on age-related cognitive decline remain largely unexplored. In the present study, we examined how microglial repopulation affects the transcriptomic profiles of cortical microglia and the decline in prefrontal cortex-dependent cognitive function in aged mice. Experimental ApproachYoung and aged male C57BL/6J mice were used in this study. Microglial depletion was induced by treatment with PLX3397, a CSF1R inhibitor, followed by microglial repopulation after drug withdrawal. Microglia isolated from the entire cerebral cortex were subjected to bulk RNA-sequencing analysis. The visual discrimination test followed by the response direction test was conducted to assess sensory learning and attentional set shifting abilities, respectively. Key ResultsRepopulated cortical microglia in aged, but not young, mice exhibited aberrant gene expression patterns, including reduced expression of microglial identity genes, reprogramming of innate and adaptive immune-related gene expression, and derepression of neuronal gene expression. Furthermore, microglial repopulation selectively impaired visual discrimination learning and attentional set shifting in aged mice. Conclusion and ImplicationsThese findings demonstrate that aging converts microglial repopulation into maladaptive reprogramming that exacerbates cognitive decline, possibly through aberrant gene expression programs. Therefore, the therapeutic potential of this approach must be carefully evaluated with respect to specific behavioral domains and disease contexts, including aging.

neuroscience↗

bioRxiv2024

Environmental DNA Surveys of Invertebrate Community on Forest Canopies Using Rainwater Analysis

Forest canopies, known for their high biodiversity, are essential for understanding forest ecosystems. Traditional methods for canopy surveys, such as tree climbing and canopy walkways, face challenges related to safety, cost, and time constraints. Environmental DNA (eDNA) analysis, which involves examining DNA from environmental samples, offers a promising alternative for these surveys. This study investigates the feasibility of using rainwater to collect eDNA from forest canopies, utilizing rains natural ability to wash away DNA from hard-to-reach areas. By comparing DNA analysis results from rainwater with conventional records obtained through visual and capture surveys, this research aims to validate the effectiveness and reliability of this method. Preliminary findings suggest that eDNA analysis from rainwater could provide an efficient approach to canopy biodiversity surveys, though further validation is required. This study marks an important first step towards developing eDNA analysis as a complementary tool for forest canopy research.

ecology↗