Transgenic mice encoding modern imaging probes: Properties and applications

Kasatkina, L.A.; Verkhusha, Vladislav V.

doi:10.1016/j.celrep.2022.110845

Cited by 9 publications

(3 citation statements)

References 124 publications

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“…Knock‐out of Blvra enzyme, responsible for converting BV to bilirubin, significantly increases endogenous BV content throughout the body and, consequently, promotes the formation of the holoform of bacteriophytochrome‐derived OTs, resulting in a situation where the majority of NIR OT molecules are assembled with endogenous BV. This expands the application of NIR OTs and NIR imaging probes (Kasatkina & Verkhusha, 2022), as many of them are derived from bacteriophytochromes.…”

Section: Discussionmentioning

confidence: 95%

iLight2: A near‐infrared optogenetic tool for gene transcription with low background activation

Baloban,

Kasatkina,

Verkhusha

2024

Protein Science

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Optogenetic tools (OTs) operating in the far‐red and near‐infrared (NIR) region offer advantages for light‐controlling biological processes in deep tissues and spectral multiplexing with fluorescent probes and OTs acting in the visible range. However, many NIR OTs suffer from background activation in darkness. Through shortening linkers, we engineered a novel NIR OT, iLight2, which exhibits a significantly reduced background activity in darkness, thereby increasing the light‐to‐dark activation contrast. The resultant optimal configuration of iLight2 components suggests a molecular mechanism of iLight2 action. Using a biliverdin reductase knock‐out mouse model, we show that iLight2 exhibits advanced performance in mouse primary cells and deep tissues in vivo. Efficient light‐controlled cell migration in wound healing cellular model demonstrates the possibility of using iLight2 in therapy and, overall, positions it as a valuable addition to the NIR OT toolkit for gene transcription applications.

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Section: Discussionmentioning

confidence: 95%

iLight2: A near‐infrared optogenetic tool for gene transcription with low background activation

Baloban,

Kasatkina,

Verkhusha

2024

Protein Science

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“…We identified DCs with typical intestinal markers in the brain, some containing bacterial fragments, strongly supporting their intestinal origin. However, we did not use a dedicated technique, such as a light convertible mouse reporter line 60 , to track direct migration of intestinal DCs into the brain. This would be extremely difficult to implement in our germ-free set-up, where all experiments are performed within custom made gnotobiotic behavioral isolators.…”

Section: Discussionmentioning

confidence: 99%

Innate immune system signaling and CD11b⁺CD11c⁺CD103⁺cell migration to the brain underlie changes in mouse behavior after microbial colonization

Philip,

Kraimi,

Zhang

et al. 2024

Preprint

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Background and AimsAccumulating evidence suggests the microbiota is a key factor in disorders of gut-brain interaction (DGBI), by affecting host immune and neural systems. However, the underlying mechanisms remain elusive due to their complexity and clinical heterogeneity of patients with DGBIs. We aimed to identify neuroimmune pathways that are critical in microbiota-gut-brain communication during de novo gut colonization.MethodsWe employed a combination of gnotobiotic and state-of-the-art microbial tools, behavioral analysis, immune and pharmacological approaches. Germ-free wild type, MyD88−/−Ticam1−/−and SCID mice were studied before and after colonization with specific pathogen-free microbiota, Altered Schaedler Flora, E. coli or S. typhimurium (permanent or transient colonizers). TLR agonists and antagonists, CCR7 antagonist or immunomodulators were used to study immune pathways. We assessed brain c-Fos, brain-derived neurotrophic factor, and dendritic and glial cells by immunofluorescence, expression of neuroimmune genes by NanoString and performed brain proteomics.ResultsBacterial monocolonization, conventionalization or administration of microbial products to germ-free mice altered mouse behavior similarly, acting through Toll-like receptor or nucleotide-binding oligomerization domain signaling. The process required CD11b+CD11c+CD103+cell activation and migration into the brain. The change in behavior did not require the continued presence of bacteria and was associated with activation of multiple neuro-immune networks in the gut and the brain.ConclusionsChanges in neural plasticity occur rapidly upon initial gut microbial colonization and involve innate immune signaling to the brain, mediated by CD11b+CD11c+CD103+cell migration. The results identify a new target with therapeutic potential for DGBIs developing in context of increased gut and blood-brain barrier permeability.HighlightsMicrobiota impairment is a key factor in disorders of gut-brain interaction (DGBI)Microbial colonization induces changes in brain and behavior via innate immunityMicrobial colonization activates multiple neuro-immune networks in gut and brainBehavioral change is mediated by CD11b+CD11c+CD103+cells migration to the brain

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“…To examine the presence and study the physiological mechanisms underlying the functioning of engram cells, scientists created a class of tools known as activity-dependent tools. These are based on the definition of engram cells and the molecular mechanisms contributing to neural activity (Bai and Suzuki, 2020 ; Colecraft, 2020 ; Demchuk et al, 2020 ; Nectow and Nestler, 2020 ; Wei et al, 2021 ; Kasatkina and Verkhusha, 2022 ; Liu et al, 2022 ; Robison and Nestler, 2022 ; Soutschek and Schratt, 2023 ). A sensory experience triggers a sensory-evoked activity, which drives a synaptic input onto the neurons and initiates membrane depolarization and calcium influx into the cytoplasm (Cohen and Greenberg, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Exploring the memory: existing activity-dependent tools to tag and manipulate engram cells

Pang,

Wu,

Chen

et al. 2024

Front. Cell. Neurosci.

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The theory of engrams, proposed several years ago, is highly crucial to understanding the progress of memory. Although it significantly contributes to identifying new treatments for cognitive disorders, it is limited by a lack of technology. Several scientists have attempted to validate this theory but failed. With the increasing availability of activity-dependent tools, several researchers have found traces of engram cells. Activity-dependent tools are based on the mechanisms underlying neuronal activity and use a combination of emerging molecular biological and genetic technology. Scientists have used these tools to tag and manipulate engram neurons and identified numerous internal connections between engram neurons and memory. In this review, we provide the background, principles, and selected examples of applications of existing activity-dependent tools. Using a combination of traditional definitions and concepts of engram cells, we discuss the applications and limitations of these tools and propose certain developmental directions to further explore the functions of engram cells.

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Transgenic mice encoding modern imaging probes: Properties and applications

Cited by 9 publications

References 124 publications

iLight2: A near‐infrared optogenetic tool for gene transcription with low background activation

iLight2: A near‐infrared optogenetic tool for gene transcription with low background activation

Innate immune system signaling and CD11b⁺CD11c⁺CD103⁺cell migration to the brain underlie changes in mouse behavior after microbial colonization

Exploring the memory: existing activity-dependent tools to tag and manipulate engram cells

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Transgenic mice encoding modern imaging probes: Properties and applications

Cited by 9 publications

References 124 publications

iLight2: A near‐infrared optogenetic tool for gene transcription with low background activation

iLight2: A near‐infrared optogenetic tool for gene transcription with low background activation

Innate immune system signaling and CD11b+CD11c+CD103+cell migration to the brain underlie changes in mouse behavior after microbial colonization

Exploring the memory: existing activity-dependent tools to tag and manipulate engram cells

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Innate immune system signaling and CD11b⁺CD11c⁺CD103⁺cell migration to the brain underlie changes in mouse behavior after microbial colonization