4-4-difluoro-4-bora-3a-4a-diaza-s-indacene and Disease-Models--Animal

Neurofibrillary tangles (NFTs), which are composed of abnormally hyperphosphorylated Tau, are one of the main pathologic hallmarks of Alzheimer's disease and other tauopathies. The fluorescent imaging probes currently used to target NFTs cannot distinguish them well from β-amyloid plaques, thus limiting their utility to diagnose diseases. Here, we developed a fused cycloheptatriene-BODIPY derivative (

Topics: Alzheimer Disease; Animals; Brain; Disease Models, Animal; Fluorescent Dyes; Mice; Mice, Transgenic; Molecular Docking Simulation; Neurofibrillary Tangles; Plaque, Amyloid; tau Proteins; Tauopathies

Amyloid formation and the deposition of the amyloid-β peptide are hallmarks of Alzheimer's disease pathogenesis. Immunotherapies using anti-amyloid-β antibodies have been highlighted as a promising approach for the prevention and treatment of Alzheimer's disease by enhancing microglial clearance of amyloid-β peptide. However, the efficiency of antibody delivery into the brain is limited, and therefore an alternative strategy to facilitate the clearance of brain amyloid is needed. We previously developed an artificial photo-oxygenation system using a low molecular weight catalytic compound. The photocatalyst specifically attached oxygen atoms to amyloids upon irradiation with light, and successfully reduced the neurotoxicity of aggregated amyloid-β via inhibition of amyloid formation. However, the therapeutic effect and mode of actions of the photo-oxygenation system in vivo remained unclear. In this study, we demonstrate that photo-oxygenation facilitates the clearance of aggregated amyloid-β from the brains of living Alzheimer's disease model mice, and enhances the microglial degradation of amyloid-β peptide. These results suggest that photo-oxygenation may represent a novel anti-amyloid-β strategy in Alzheimer's disease, which is compatible with immunotherapy.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Boron Compounds; Brain; Disease Models, Animal; Humans; Mice; Microglia; Phototherapy; Protein Aggregates

J-aggregation is an efficient strategy for the development of fluorescent imaging agents in the second near-infrared window. However, the design of the second near-infrared fluorescent J-aggregates is challenging due to the lack of suitable J-aggregation dyes. Herein, we report meso-[2.2]paracyclophanyl-3,5-bis-N,N-dimethylaminostyrl BODIPY (PCP-BDP2) as an example of BODIPY dye with J-aggregation induced the second near-infrared fluorescence. PCP-BDP2 shows an emission maximum at 1010 nm in the J-aggregation state. Mechanism studies reveal that the steric and conjugation effect of the PCP group on the BODIPY play key roles in the J-aggregation behavior and photophysical properties tuning. Notably, PCP-BDP2 J-aggregates can be utilized for lymph node imaging and fluorescence-guided surgery in the nude mouse, which demonstrates their potential clinical application. This study demonstrates BODIPY dye as an alternate J-aggregation platform for developing the second near-infrared imaging agents.

Topics: Animals; Boron Compounds; Cell Line, Tumor; Disease Models, Animal; Fluorescence; Fluorescent Dyes; Humans; Infrared Rays; Intravital Microscopy; Lymphatic System; Mice; Optical Imaging; Peritoneal Neoplasms; Video-Assisted Surgery

In this study, a series of organo difluoroboron probes with a BF2 benzamide moiety was designed, prepared and evaluated. Among them, 2c displayed the best optical and biological properties, and may be used as a useful near-infrared fluorescent probe for the detection of Aβ plaques and neurofibrillary tangles in AD.

Topics: Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Animals; Benzamides; Biological Transport; Biosensing Techniques; Boron Compounds; Disease Models, Animal; Female; Fluorescent Dyes; Hippocampus; Humans; Hydrophobic and Hydrophilic Interactions; Male; Mice; Optical Imaging; Presenilin-1; Protein Binding; Protein Conformation; Spectrometry, Fluorescence; Spectroscopy, Near-Infrared; tau Proteins

Delving deeper is possible in whole-body in vivo imaging using a super-bright membrane-targeting BODIPY dye (BD). The dye was used to monitor homing of ex vivo fluorescently labelled neutrophils to an injured liver of dark-pigmented C57BL/6 mice. In vivo imaging system (IVIS) data conclusively showed an enhanced signal intensity and a higher signal-to-noise ratio in mice receiving neutrophils labelled with the BD dye relative to those labelled with a gold standard dye at 2 h post in vivo administration of fluorescently labelled cells. Fluorescence-activated cell sorting (FACS) confirmed that BD is nontoxic, and an exceptional cell labelling dye that opens up precision deep-organ in vivo imaging of inflammation in mice routinely used for biomedical research. The origin of enhanced performance is identified with the molecular structure and the distinct localisation of the dye within cells that enable remarkable changes in its optical parameters.

Topics: Acute Lung Injury; Animals; Boron Compounds; Cell Line; Disease Models, Animal; Flow Cytometry; Fluorescent Dyes; Liver; Mice, Inbred C57BL; Models, Molecular; Neutrophils; Optical Imaging

Inflammation is a hallmark of epileptogenic brain tissue. Previously, we have shown that inflammation in epilepsy can be delineated using systemically-injected fluorescent and magnetite- laden nanoparticles. Suggested mechanisms included distribution of free nanoparticles across a compromised blood-brain barrier or their transfer by monocytes that infiltrate the epileptic brain.. In the current study, we evaluated monocytes as vehicles that deliver nanoparticles into the epileptic brain. We also assessed the effect of epilepsy on the systemic distribution of nanoparticleloaded monocytes.. The in vitro uptake of 300-nm nanoparticles labeled with magnetite and BODIPY (for optical imaging) was evaluated using rat monocytes and fluorescence detection. For in vivo studies we used the rat lithium-pilocarpine model of temporal lobe epilepsy. In vivo nanoparticle distribution was evaluated using immunohistochemistry.. 89% of nanoparticle loading into rat monocytes was accomplished within 8 hours, enabling overnight nanoparticle loading ex vivo. The dose-normalized distribution of nanoparticle-loaded monocytes into the hippocampal CA1 and dentate gyrus of rats with spontaneous seizures was 176-fold and 380-fold higher compared to the free nanoparticles (p<0.05). Seizures were associated with greater nanoparticle accumulation within the liver and the spleen (p<0.05).. Nanoparticle-loaded monocytes are attracted to epileptogenic brain tissue and may be used for labeling or targeting it, while significantly reducing the systemic dose of potentially toxic compounds. The effect of seizures on monocyte biodistribution should be further explored to better understand the systemic effects of epilepsy.

Topics: Animals; Boron Compounds; Disease Models, Animal; Drug Delivery Systems; Epilepsy, Temporal Lobe; Fluorescent Dyes; Hippocampus; Inflammation; Kidney; Lithium Chloride; Liver; Magnetite Nanoparticles; Male; Monocytes; Pilocarpine; Rats, Wistar; Spleen

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Boron Compounds; Brain; Disease Models, Animal; Fluorescent Dyes; Male; Mice; Mice, Transgenic; Plaque, Amyloid; Spectrometry, Fluorescence

Neuronal accumulation of tau aggregates is a pathological hallmark in multiple neurodegenerative disorders, collectively called tauopathies. A tau aggregation sensor that can monitor abnormal tau aggregation in neurons would facilitate the study of tau aggregation processes and the discovery of tau aggregation blockers. Here, we describe a BODIPY-fluorescence sensor (BD-tau) that selectively responds to pathological tau aggregates in live cells.

Topics: Animals; Boron Compounds; Cell Line; Disease Models, Animal; Fluorescent Dyes; Humans; Mice; Mice, Transgenic; Molecular Structure; Neurons; Optical Imaging; Protein Aggregates; tau Proteins

The proportions of body fat and fat-free mass are determining factors of adiposity-associated diseases. Work in Caenorhabditis elegans has revealed evolutionarily conserved pathways of fat metabolism. Nevertheless, analysis of body composition and fat distribution in the nematodes has only been partially unraveled because of methodological difficulties. We characterized metabolic C. elegans mutants by using novel and feasible BODIPY 493/503-based fat staining and flow cytometry approaches. Fixative as well as vital BODIPY staining procedures visualize major fat stores, preserve native lipid droplet morphology, and allow quantification of fat content per body volume of individual worms. Colocalization studies using coherent anti-Stokes Raman scattering microscopy, Raman microspectroscopy, and imaging of lysosome-related organelles as well as biochemical measurement confirm our approaches. We found that the fat-to-volume ratio of dietary restriction, TGF-β, and germline mutants are specific for each strain. In contrast, the proportion of fat-free mass is constant between the mutants, although their volumes differ by a factor of 3. Our approaches enable sensitive, accurate, and high-throughput assessment of adiposity in large C. elegans populations at a single-worm level.

Topics: Adipose Tissue; Adiposity; Animals; Azo Compounds; Boron Compounds; Caenorhabditis elegans; Disease Models, Animal; Fixatives; Flow Cytometry; Fluorescence; Germ-Line Mutation; High-Throughput Screening Assays; Lipid Metabolism; Microscopy; Obesity; Species Specificity; Spectrum Analysis, Raman; Staining and Labeling; Transforming Growth Factor beta

To determine the distribution of endotracheally administered surfactant at the alveolar level in an animal model of acute respiratory distress syndrome.. Prospective, randomized animal study.. Research laboratory of a university hospital.. Seventy-one male Sprague-Dawley rats, weighing 330-370 g.. To measure surfactant distribution in vitro, a glass trough mimicking dichotomic lung anatomy was used to determine the spreading properties of bovine lung surfactant extract supplemented with fluorescent Bodipy-labeled surfactant protein B. To measure surfactant distribution in vivo, rats were anesthetized, and lipopolysaccharide was aerosolized (12 mg/kg body weight) to induce lung injury resembling acute respiratory distress syndrome; in control rats, buffered saline was aerosolized. Twenty-four hours later rats were anesthetized, tracheotomized, and mechanically ventilated (peak airway pressure = 20 mbar; positive end-expiratory pressure = 6 mbar; inspiration time = expiration time = 0.6 sec; Fio2 = 50%). Surfactant (bovine lung surfactant extract, supplemented with fluorescent Bodipy-labeled surfactant protein B; 50 mg/kg body weight) was applied as a bolus; in control rats, saline was administered as a bolus. Rats were ventilated for 5, 15, 30, or 60 mins (n = 8 or 9 for each group). Then, lungs were excised and sliced. Lung slices, divided into aerated (open), underinflated (dystelectatic), or collapsed (atelectatic) alveolar areas, were examined by both light and fluorescence microscopy.. In vitro experiments revealed that surfactant spread independent of glass trough geometry and lowered the surface tension to equilibrium values (25 mN/m) within a few seconds. In vivo experiments showed that administered surfactant distributed preferentially into underinflated and aerated alveolar areas. Furthermore, surfactant distribution was not affected by length of mechanical ventilation.. When conventional mechanical ventilation was used in lipopolysaccharide-induced lung injury, surfactant preferentially distributed into underinflated and aerated alveolar areas. Because surfactant rarely reached collapsed alveolar areas, methods aiding in alveolar recruitment (e.g., open lung concept or body positioning) should precede surfactant administration.

Topics: Animals; Boron Compounds; Disease Models, Animal; Fluorescent Dyes; Humans; Infant, Newborn; Male; Microscopy, Fluorescence; Pulmonary Alveoli; Rats; Rats, Sprague-Dawley; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Surface-Active Agents; Tissue Distribution