Biology subjects

Spring, B. Q.

Publications and source records attributed to Spring, B. Q..

2 recordsLinked to original sources

bioRxiv2026

Partial sleep deprivation diminishes and uncouples neuronal activity and energy metabolism in the live mouse hippocampus

Sleep disorders and wakefulness constitute a pronounced and pervasive health risk that contributes to numerous cerebral pathologies such as stroke, depression, and neurodegenerative disorders. The hippocampus (HC) plays vital roles in learning and memory and is especially susceptible to the pathological insults imposed by sleep deprivation (SD). While SD disrupts neuronal network signaling and triggers inflammatory processes, the impact of SD on metabolism within the HC presently remains poorly understood. In this study, we assessed the progressive and cumulative effects of partial SD in the live mouse HC CA1 region using two-photon microscopy. Using a custom-designed implantable cannula enabling direct HC visualization and administration of dyes and pharmacological agents directly to HC tissue, we longitudinally monitored spontaneous neuronal activity and partial pressure of oxygen (pO2) within HC CA1 tissue before and during a 7-day period of partial SD and after a 7- day period of recovery. Our results revealed a progressive decline in spontaneous neural activity, alongside sustained elevation in tissue pO2; during the 7-day partial SD period. Notably, after 7 days of recovery, neuronal activity did not return to baseline, and tissue oxygenation continued to increase. Our findings emphasize chronic SD's cumulative and enduring impairments to neuronal function and metabolism in the HC and reveal uncoupling between metabolic and functional recovery that outlasts the sleep restriction period.

neuroscience↗

bioRxiv2022

Sparse-spectral microendoscopy for real-time visualization of tumor cell phenotype and microenvironment spatial heterogeneity in vivo

Cancer heterogeneity and its transformation with time propels treatment resistance and confounds patient outcomes. The inability to monitor in vivo the low abundance, heterocellular phenotypes that resist treatment and ultimately lead to patient death limits the ability to design precision therapies. Here we overcome limitations in multiplexed fluorescence phenotyping to introduce real-time, cellular resolution visualization of tumor heterogeneity in vivo. This method was performed to simultaneously map for the first time 5 individual biomarkers of stemness, proliferation, metabolism, leukocytes and angiogenesis deep within the peritoneal cavities of micrometastatic cancer mouse models at 17 frames per second (fps). The newly developed imaging system revealed distinct cancer cell phenotype-immune cell spatial correlations and clearly visualized the dynamic spatial response of resistant cancer cell niches following treatment. Furthermore, wide-field datasets were generated to facilitate derivation of a mathematical framework for quantifying biomarker spatial variation and thereby overcoming the area restrictions of conventional tumor biopsy. These results pave the way for real-time identification of cancer cell phenotypes in a clinical setting, on which optimized treatment regimens can be based for personalized treatment and precision therapy e.g., tumor margin determination during surgical resection. Additionally, this modality can be used to obtain more fundamental insights into tumor heterogeneity and how treatments affect the molecular and cellular responses of patient-specific disease.

bioengineering↗