Biology subjects

Duran-Aniotz, C.

Publications and source records attributed to Duran-Aniotz, C..

3 recordsLinked to original sources

bioRxiv2025

XBP1s as a Therapeutic Target to Preserve Retinal Function During Aging and Neurodegeneration

Loss of physiological complexity, characterized by reduced adaptive multiscale coordination among system components, is increasingly recognized as a hallmark of aging and neurodegenerative disease. The retina, a window into the brain, offers a unique, accessible platform to monitor neurodegenerative disorders such as Alzheimers disease (AD). Here, we investigate the therapeutic potential of the unfolded protein response transcription factor XBP1s in preserving retinal function during aging and AD-related pathology in murine models. Using micro-electroretinography with multielectrode arrays, we recorded retinal responses to chirp and white noise stimuli in four mouse models: wild-type (WT), XBP1s-overexpressing (TgXBP1s), AD model (5xFAD), and their crossbreed (TgXBP1s/5xFAD) at approximately 3 and 7 months of age. We assessed retinal signals through entropy-based complexity measures and wavelet coherence between stimulus and response. While WT and 5xFAD mice exhibited age-related decline in retinal complexity, TgXBP1s and TgXBP1s/5xFAD mice maintained higher complexity levels and increased Wcoh in adulthood, indicating functional preservation. These results demonstrate that sus-tained XBP1s expression protects retinal electrophysiological integrity and highlight the retinas value as a scalable, noninvasive biomarker platform to evaluate therapeutic efficacy targeting neurodegenerative mechanisms.

neuroscience↗

bioRxiv2022

Multiscale Entropy Analysis of Retinal Signals Reveals Reduced Complexity in a Mouse Model of Alzheimer's Disease

Alzheimers disease (AD) is one of the most significant health challenges of our time, affecting a growing number of the elderly population. In recent years, the retina has received increased attention as a candidate for AD biomarkers since it appears to manifest the pathological signatures of the disease. Therefore, its electrical activity may hint at AD-related physiological changes. However, it is unclear how AD affects retinal electrophysiology and what tools are more appropriate to detect these possible changes. In this study, we used entropy tools to estimate the complexity of the dynamics of healthy and diseased retinas at different ages. We recorded microelectroretinogram responses to visual stimuli of different nature from retinas of young and adult, wild-type and 5xFAD -an animal model of AD- mice. To estimate the complexity of signals, we used the multiscale entropy approach, which calculates the entropy at several time scales using a coarse graining procedure. We found that young retinas had more complex responses to different visual stimuli. Further, the responses of young, wild-type retinas to natural-like stimuli exhibited significantly higher complexity than young, 5xFAD retinas. Our findings support a theory of complexity-loss with aging and disease and can have significant implications for early AD diagnosis.

neuroscience↗

bioRxiv2020

Control of mammalian brain aging by the unfolded protein response (UPR)

Aging is the major risk factor for the development of dementia and neurodegenerative disorders, and the aging brain manifests severe deficits in buffering capacity by the proteostasis network. Accordingly, we investigated the significance of the unfolded protein response (UPR), a major signaling pathway that copes with endoplasmic reticulum (ER) stress, to normal mammalian brain aging. Genetic disruption of ER stress sensor IRE1 accelerated cognitive and motor dysfunction during aging. Exogenous bolstering of the UPR by overexpressing an active form of the transcription factor XBP1 restored synaptic and cognitive function in addition to reducing cell senescence. Remarkably, proteomic profiling of hippocampal tissue indicated that XBP1s expression corrected age-related alterations in synaptic function. Collectively, our data demonstrate that strategies to manipulate the UPR sustain healthy brain aging. One Sentence SummaryThe IRE1/XBP1 pathway dictates when and how brain function declines during aging.

neuroscience↗