scholarly journals Ca2+ Imaging With Two-photon Microscopy to Detect the Disruption of Brain Function in Mice Administered With Neonicotinoid Insecticides

2021 ◽  
Author(s):  
Anri Hirai ◽  
Shouta Sugio ◽  
Collins Nimako ◽  
Shouta Nakayama ◽  
Keisuke Kato ◽  
...  
Keyword(s):  
Lethal Dose ◽  
Neuronal Population ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Highly Sensitive Detection ◽  
Neonicotinoid Pesticides ◽  
The Brain

Abstract Neonicotinoid pesticides are insecticides that are insecticides that reportedly have untargeted effects on bees and dragonflies causing a reduction in numbers. Neonicotinoids act as neuroreceptor modulators, and some studies have reported their association with neurodevelopmental disorders. However, the effect of neonicotinoids on the central nervous system has not yet been identified. Herein, we conducted in vivo Ca2+ imaging using a two-photon microscope to detect abnormal activity of neuronal circuits in the brain using a neonicotinoid. The oral administration of acetamiprid (ACE) (20 mg/kg body weight [bw]) in mature mice with a less than the no-observed-adverse-effect level (NOAEL) and a tenth or half of the median lethal dose (LD50) of nicotine (0.33 or 1.65 mg/kg bw, respectively), as a typical nAChRs agonist, increased anxiety-like behavior associated with altered activities of the neuronal population in the somatosensory cortex. Furthermore, we detected ACE and metabolites in the brain 1 h after ACE administration. The results suggested that in vivo Ca2+ imaging using a two-photon microscope enabled the highly sensitive detection of neurotoxicant-mediated brain disturbance of nerves.

scholarly journals P02.08 Visualizing tumor cell - lymphocyte interactions in the brain metastatic cascade using in vivo two photon microscopy

2018 ◽  
Vol 20 (suppl_3) ◽  
pp. iii273-iii273
Author(s):  
M Piechutta ◽  
A S Berghoff ◽  
M A Karreman ◽  
K Gunkel ◽  
W Wick ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Metastatic Cascade ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
The Brain

scholarly journals IMMU-26. VISUALIZING TUMOR CELL - LYMPHOCYTE INTERACTIONS IN THE BRAIN METASTATIC CASCADE USING IN VIVO TWO PHOTON MICROSCOPY

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi126-vi127
Author(s):  
Manuel Piechutta ◽  
Anna Berghoff ◽  
Matthia Karreman ◽  
Katharina Gunkel ◽  
Wolfgang Wick ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Metastatic Cascade ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
The Brain

scholarly journals Post-capillary venules is the locus for transcytosis of therapeutic nanoparticles to the brain

2020 ◽  
Author(s):  
Krzysztof Kucharz ◽  
Kasper Kristensen ◽  
Kasper Bendix Johnsen ◽  
Mette Aagaard Lund ◽  
Micael Lønstrup ◽  
...  
Keyword(s):  
Drug Carrier ◽  
Basement Membranes ◽  
List Type ◽  
Biologic Drugs ◽  
Large Molecules ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Resolution Imaging ◽  
The Brain

SUMMARYTreatments of neurodegenerative diseases require biologic drugs to be actively transported across the blood-brain barrier (BBB). To answer outstanding questions regarding transport mechanisms, we determined how and where transcytosis occurs at the BBB. Using two-photon microscopy, we characterized the transport of therapeutic nanoparticles at all steps of delivery to the brain and at the nanoscale resolution in vivo. Transferrin receptor-targeted nanoparticles were taken up by endothelium at capillaries and venules, but not at arterioles. The nanoparticles moved unobstructed within endothelial cells, but transcytosis across the BBB occurred only at post-capillary venules, where endothelial and glial basement membranes form a perivascular space that can accommodate biologics. In comparison, transcytosis was absent in capillaries with closely apposed basement membranes. Thus, post-capillary venules, not capillaries, provide an entry point for transport of large molecules across the BBB, and targeting therapeutic agents to this locus may be an effective way for treating brain disorders.HIGHLIGHTSIntegration of drug carrier nanotechnology with two-photon microscopy in vivoReal-time nanoscale-resolution imaging of nanoparticle transcytosis to the brainDistinct trafficking pattern in the endothelium of cerebral venules and capillariesVenules, not capillaries, is the locus for brain uptake of therapeutic nanoparticles

scholarly journals Post-capillary venules are the key locus for transcytosis-mediated brain delivery of therapeutic nanoparticles

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Krzysztof Kucharz ◽  
Kasper Kristensen ◽  
Kasper Bendix Johnsen ◽  
Mette Aagaard Lund ◽  
Micael Lønstrup ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
Drug Carriers ◽  
Perivascular Space ◽  
Brain Uptake ◽  
Brain Delivery ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Basic Understanding ◽  
The Brain

AbstractEffective treatments of neurodegenerative diseases require drugs to be actively transported across the blood-brain barrier (BBB). However, nanoparticle drug carriers explored for this purpose show negligible brain uptake, and the lack of basic understanding of nanoparticle-BBB interactions underlies many translational failures. Here, using two-photon microscopy in mice, we characterize the receptor-mediated transcytosis of nanoparticles at all steps of delivery to the brain in vivo. We show that transferrin receptor-targeted liposome nanoparticles are sequestered by the endothelium at capillaries and venules, but not at arterioles. The nanoparticles move unobstructed within endothelium, but transcytosis-mediated brain entry occurs mainly at post-capillary venules, and is negligible in capillaries. The vascular location of nanoparticle brain entry corresponds to the presence of perivascular space, which facilitates nanoparticle movement after transcytosis. Thus, post-capillary venules are the point-of-least resistance at the BBB, and compared to capillaries, provide a more feasible route for nanoparticle drug carriers into the brain.

scholarly journals Whole-brain imaging and characterization of Drosophila brains based on one-, two-, and three-photon excitations

2018 ◽  
Author(s):  
Kuo-Jen Hsu ◽  
Yen-Yin Lin ◽  
Ann-Shyn Chiang ◽  
Shi-Wei Chu
Keyword(s):  
High Speed ◽  
Optical Sectioning ◽  
Whole Brain ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Functional Connectome ◽  
Molecular Specificity ◽  
The Brain

AbstractTo study functional connectome, optical microscopy provides the advantages of in vivo observation, molecular specificity, high-speed acquisition, and sub-micrometer spatial resolution. Now, the most complete single-neuron-based anatomical connectome is built upon Drosophila; thus it will be a milestone to achieve whole-brain observation with sub-cellular resolution in living Drosophila. Surprisingly, two-photon microscopy cannot penetrate through the 200-μm-thick brain, due to the extraordinarily strong aberration/scattering from tracheae. Here we achieve whole-Drosophila-brain observation by degassing the brain or by using three-photon microscopy at 1300-nm, while only the latter provides in vivo feasibility, reduced aberration/scattering and exceptional optical sectioning capability. Furthermore, by comparing one-photon (488-nm), two-photon (920-nm), and three-photon (1300-nm) excitations in the brain, we not only demonstrate first quantitative reduction of both scattering and aberration in trachea-filled tissues, but unravel that the contribution of aberration exceeds scattering at long wavelengths. Our work paves the way toward constructing functional connectome in a living Drosophila.

scholarly journals In Vivo Evaluation of the Chronic Oral Toxicity of the Marine Toxin Palytoxin

Toxins ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 489
Author(s):  
Andrea Boente-Juncal ◽  
Sandra Raposo-García ◽  
Carmen Vale ◽  
M. Carmen Louzao ◽  
Paz Otero ◽  
...  
Keyword(s):  
Oral Administration ◽  
Chronic Toxicity ◽  
Lethal Dose ◽  
Oral Toxicity ◽  
In Vivo Evaluation ◽  
Marine Toxin ◽  
Adverse Effect Level ◽  
Marine Products ◽  
Effect Level

Palytoxin (PLTX) is one of the most poisonous substances known to date and considered as an emergent toxin in Europe. Palytoxin binds to the Na+-K+ ATPase, converting the enzyme in a permeant cation channel. This toxin is known for causing human fatal intoxications associated with the consumption of contaminated fish and crustaceans such as crabs, groupers, mackerel, and parrotfish. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Different reports have previously explored the acute oral toxicity of PLTX in mice. Although the presence of palytoxin in marine products is currently not regulated in Europe, the European Food Safety Authority expressed its opinion on PLTX and demanded assessment for chronic toxicity studies of this potent marine toxin. In this study, the chronic toxicity of palytoxin was evaluated after oral administration to mice by gavage during a 28-day period. After chronic exposure of mice to the toxin, a lethal dose 50 (LD50) of 0.44 µg/kg of PLTX and a No-Observed-Adverse-Effect Level (NOAEL) of 0.03 µg/kg for repeated daily oral administration of PLTX were determined. These results indicate a much higher chronic toxicity of PLTX and a lower NOAEL than that previously described in shorter treatment periods, pointing out the need to further reevaluate the levels of this compound in marine products.

In vivo imaging of liver injury and regeneration by functional two-photon microscopy

2016 ◽  
Vol 54 (12) ◽  
pp. 1343-1404
Author(s):  
A Ghallab ◽  
R Reif ◽  
R Hassan ◽  
AS Seddek ◽  
JG Hengstler
Keyword(s):  
Liver Injury ◽  
In Vivo Imaging ◽  
Two Photon Microscopy ◽  
Two Photon

Sensory Transmission is Bi-directionally Modulated by Astrocytic Ca2+ in Barrel Cortex of Behaving Mice

2021 ◽  
Author(s):  
Simeng Gu ◽  
Wei Wang ◽  
Kuan Zhang ◽  
Rou Feng ◽  
Naling Li ◽  
...  
Keyword(s):  
Sensory Input ◽  
Barrel Cortex ◽  
Synaptic Function ◽  
Metabolic Clearance ◽  
Sleep State ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Sensory Transmission

Abstract Different effects of astrocyte during sleep and awake have been extensively studied, especially for metabolic clearance by the glymphatic system, which works during sleep and stops working during waking states. However, how astrocytes contribute to modulation of sensory transmission during sleep and awake animals remain largely unknown. Recent advances in genetically encoded Ca2+ indicators have provided a wealth of information on astrocytic Ca2+, especially in their fine perisynaptic processes, where astrocytic Ca2+ most likely affects the synaptic function. Here we use two-photon microscopy to image astrocytic Ca2+ signaling in freely moving mice trained to run on a wheel in combination with in vivo whole-cell recordings to evaluate the role of astrocytic Ca2+ signaling in different behavior states. We found that there are two kinds of astrocytic Ca2+ signaling: a small long-lasting Ca2+ increase during sleep state and a sharp widespread but short-long-lasting Ca2+ spike when the animal was awake (fluorescence increases were 23.2 ± 14.4% for whisker stimulation at sleep state, compared with 73.3 ± 11.7% for at awake state, paired t-test, p < 0.01). The small Ca2+ transients decreased extracellular K+, hyperpolarized the neurons, and suppressed sensory transmission; while the large Ca2+ wave enhanced sensory input, contributing to reliable sensory transmission in aroused states. Locus coeruleus activation works as a switch between these two kinds of astrocytic Ca2+ elevation. Thus, we show that cortical astrocytes play an important role in processing of sensory input. These two types of events appear to have different pharmacological sources and may play a different role in facilitating the efficacy of sensory transmission.

Quantum Dots assisted and NIR-II Emissive In Vivo Two-photon microscopy

2021 ◽  
Author(s):  
Huwei Ni ◽  
Yalun Wang ◽  
Tao Tang ◽  
Wenbin Yu ◽  
Dongyu Li ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Two Photon Microscopy ◽  
Two Photon
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