Biology subjects

Gattegno, R.

Publications and source records attributed to Gattegno, R..

5 recordsLinked to original sources

bioRxiv2025

Nanobubble based sonobiopsy reveals circulating protein signatures of BBB opening and glioblastoma

Focused ultrasound (FUS) and microbubbles can transiently increase blood brain barrier (BBB) permeability, yet verification of BBB opening (BBBO) relies mainly on contrast-enhanced MRI, offering limited insight into the molecular consequences of barrier modulation. Sonobiopsy, which uses FUS induced BBBO to release brain derived molecules into the bloodstream, provides a molecular readout from blood samples. Nanobubbles (NBs) are smaller agents that circulate more effectively in the brain microvasculature and have shown enhanced BBBO in capillaries. Here, NB-mediated proteomic sonobiopsy is used to improve biomarker efflux and increase molecular sensitivity, with the goal of defining the molecular signature produced by BBBO in healthy and glioblastoma (GBM) models, and distinguishing biomarkers associated with tumor pathology from BBBO biomarkers. Plasma collected before and after NB-mediated FUS underwent data-independent acquisition-based mass spectrometry, revealing post-BBBO changes in healthy and tumor bearing mice. In healthy cohorts, 77 proteins were reproducibly altered after BBBO. Six proteins (Dpysl3, Myl1, Mybpc1, Vsig4, Krt33a, Krtap6-5) were detectable only after BBBO in healthy mice. In 005 glioma bearing mice, the BBBO signature identified in healthy animals was preserved, and comparison with matched shams isolated tumor specific effects. Three proteins, Itih4, Lrg1, and Hp, rose significantly after BBBO only in GBM and reached higher post treatment levels than in shams, nominating candidate GBM-associated markers accessible via blood. These findings establish NB-mediated proteomic sonobiopsy as a promising method for BBBO verification and for detecting GBM associated protein signals, supporting the development of scalable BBBO confirmation and protein-based diagnostics in neuro oncology. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/692317v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@d0186aorg.highwire.dtl.DTLVardef@1f2fe8borg.highwire.dtl.DTLVardef@25921forg.highwire.dtl.DTLVardef@9c3566_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2023

Enhanced capillary delivery with nanobubble-mediated blood-brain barrier opening and advanced high resolution vascular segmentation

Overcoming the blood-brain barrier (BBB) is essential to enhance brain therapy. Here, we utilized nanoscale nanobubbles with focused ultrasound for targeted and improved BBB opening in mice. A microscopy method assessed BBB opening at a single blood vessel resolution employing a dual-dye labeling technique using green fluorescent molecules to label blood vessels and Evans blue brain-permeable dye for quantifying BBB extravasation. A UNET-based deep learning architecture enabled blood vessels segmentation, delivering comparable accuracy to manual segmentation with a significant time reduction. Segmentation outcomes were applied to the Evans blue channel to quantify extravasation of each blood vessel. Results were compared to microbubble-mediated BBB opening, where reduced extravasation was observed in capillaries with 2-6m diameter. In comparison, nanobubbles yield an improved opening in these capillaries, and equivalent efficacy to that of microbubbles in larger vessels. These results indicate the potential of nanobubbles to serve as enhanced agents for BBB opening, amplifying bioeffects in capillaries while preserving comparable opening in larger vessels.

bioengineering↗

bioRxiv2023

Local activation of CA1 pyramidal cells induces theta phase precession

Hippocampal theta phase precession is involved in spatiotemporal coding and generating multineural spike sequences, but how precession originates remains unresolved. To determine whether precession can be generated directly in CA1 and disambiguate multiple competing mechanisms, we used optogenetic activation to impose artificial place fields in pyramidal cells of mice running on a linear track. More than a third of the CA1 artificial fields exhibited synthetic precession that persisted for a full cycle. In contrast, artificial fields in the parietal cortex did not exhibit synthetic precession. The findings are incompatible with precession models based on inheritance, spreading activation, dual-input, or inhibition-excitation summation. Thus, a precession generator resides locally within CA1.

neuroscience↗

bioRxiv2023

Positive and biphasic extracellular waveforms correspond to return currents and axonal spikes

Multiple biophysical mechanisms may generate non-negative extracellular waveforms during action potentials, but the origin and prevalence of positive spikes and biphasic spikes in the intact brain are unknown. Using extracellular recordings from densely-connected cortical networks in freely-moving mice, we find that a tenth of the waveforms are non-negative. Positive phases of non-negative spikes occur in synchrony or just before wider same-unit negative spikes. Narrow positive spikes occur in isolation in the white matter. Isolated biphasic spikes are narrower than negative spikes, occurring right after spikes of verified inhibitory units. In CA1, units with dominant non-negative spikes exhibit place fields, phase precession, and phase-locking to ripples. Thus, near-somatic narrow positive extracellular potentials correspond to return currents, and isolated non-negative spikes correspond to axonal potentials. Identifying non-negative extracellular waveforms that correspond to non-somatic compartments during spikes can enhance the understanding of physiological and pathological neural mechanisms in intact animals.

neuroscience↗

bioRxiv2022

Hybrid offspring of C57BL/6J mice exhibit improved properties for neurobehavioral research

C57BL/6 is the most commonly used mouse strain in neurobehavioral research, serving as a background for multiple transgenic lines. However, C57BL/6 exhibit behavioral and sensorimotor disadvantages that worsen with age. We bred FVB/NJ females and C57BL/6J males to generate first-generation hybrid offspring, (FVB/NJ x C57BL/6J)F1. The hybrid mice exhibit reduced anxiety-like behavior, improved learning, and enhanced long-term spatial memory. In contrast to both progenitors, older hybrids maintain sensorimotor performance and exhibit improved long-term memory. The hybrids are larger than C57BL/6J, exhibiting enhanced running behavior on a linear track during freely-moving electrophysiological recordings. Hybrids exhibit typical rate and phase coding of space by CA1 pyramidal cells. Hybrids generated by crossing FVB/NJ females with transgenic males of a C57BL/6 background support optogenetic neuronal control in neocortex and hippocampus. The hybrid mice provide an improved model for neurobehavioral studies combining complex behavior, electrophysiology, and genetic tools readily available in C57BL/6 mice.

neuroscience↗