Biology subjects

Albensi, B. C.

Publications and source records attributed to Albensi, B. C..

2 recordsLinked to original sources

bioRxiv2024

Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer's Disease: Linking Cellular Dysfunction to Cognitive Decline

Macroautophagy and mitophagy are critical processes in Alzheimers disease (AD), yet their links to behavioral outcomes, particularly sex-specific differences, are not fully understood. This study investigates autophagy (LC3B-II, SQSTM1) and mitophagy (BNIP3L, BNIP3, BCL2L13) markers in the cortex and hippocampus of male and female 3xTg-AD mice, using western blotting, transmission electron microscopy (TEM), and behavioral tests (novel object recognition and novel object placement). Significant sex-specific differences emerged: female 3xTg-AD mice exhibited autophagosome accumulation due to impaired degradation in the cortex, while males showed fewer autophagosomes, especially in the hippocampus, without significant degradation changes. TEM analyses demonstrated variations in mitochondrial and mitophagosome numbers correlated with memory outcomes. Females had enhanced mitophagy, with higher BNIP3L and BCL2L13 levels, whereas males showed elevated BNIP3 dimers. Cognitive deficits in females correlated with mitochondrial dysfunction in the cortex, while in males, higher LC3B-II levels associated positively with cognitive performance, suggesting protective autophagy effects. Using machine learning, we predicted mitophagosome and mitochondrial numbers based on behavioral data, pioneering a predictive approach to cellular outcomes in AD. These findings underscore the importance of sex-specific regulation of autophagy and mitophagy in AD and support personalized therapeutic approaches targeting these pathways. Integrating machine learning emphasizes its potential to advance neurodegenerative research. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/621097v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1e50ceeorg.highwire.dtl.DTLVardef@b41ac0org.highwire.dtl.DTLVardef@4863d3org.highwire.dtl.DTLVardef@91b2d0_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphical AbstractSex-specific differences in autophagy and mitophagy regulation in Alzheimers disease (AD) are highlighted. Female 3xTg-AD mice show autophagosome accumulation and cognitive deficits, while males exhibit variations in mitophagy markers and behavior.

neuroscience↗

bioRxiv2023

Platelet extracellular vesicles and their mitochondrial content significantly improve survival and cytokine levels when transfused into mice with sepsis or H1N1 infections

BACKGROUNDMitochondrial transplantation has recently gained prominence as a novel technique primarily focused on addressing ischemiareperfusion injuries and rare mitochondrial mutation diseases. Platelets, abundant in the bloodstream, play a crucial role in immune function. Upon activation, platelets release mitochondria encapsulated within extracellular vesicles, here referred to as "mitlets". These mitlets exhibit a preference for being internalized by immune cells circulating in the bloodstream, enhancing their cellular energetics. Herein, we hypothesized that the transplantation of mitlets between young animals and aged animals may exert a significant influence on the progression of infectious diseases. STUDY DESIGN AND METHODSIn this study, murine models of Influenza H1N1 infection and sepsis were employed to investigate disease dynamics. Specifically, mitlets isolated from young and healthy mice were transplanted into cohorts of mice of the same age afflicted by H1N1 infection, or into aged mice subjected to polymicrobial infection and sepsis. Survival outcomes and the quantification of cytokine levels were assessed across experimental groups to elucidate the potential therapeutic effects of mitlet transplantation. RESULTSIn the matched-age H1N1 infection model, as predicted, mitlet transplantation did not yield a statistically significant improvement in survival, although it did show a trend towards a reduction in the circulating inflammatory cytokine burden. In the young-to-old sepsis model, the transplantation of mitlets was associated with a significant enhancement in survival rates and a substantial reduction in bacterial loads and circulating cytokine levels. DISCUSSIONOur findings suggest that mitochondrial transplantation may constitute a safe and promising avenue for enhancing the immune systems capacity to counter infectious threats. This pilot investigation sets the stage for further exploration. It is plausible that in the future, immune senescence resulting from diminished mitochondrial energy production could be ameliorated through such transplantation interventions. As a consequence, this approach holds substantial potential as a novel immunotherapeutic strategy for the management of infectious diseases.

molecular biology↗