Brain-on-a-chip: an emerging platform for studying the nanotechnology-biology interface for neurodegenerative disorders

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 18, 2024

Language: Английский

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Neuromodulator and neuropeptide sensors and probes for precise circuit interrogation in vivo

Science, Journal Year: 2024, Volume and Issue: 385(6716)

Published: Sept. 26, 2024

To determine how neuronal circuits encode and drive behavior, it is often necessary to measure manipulate different aspects of neurochemical signaling in awake animals. Optogenetics calcium sensors have paved the way for these types studies, allowing perturbation readout spiking activity within genetically defined cell types. However, methods lack ability further disentangle roles individual neuromodulator neuropeptides on behavior. We review recent advances chemical biology tools that enable precise spatiotemporal monitoring control over neuroeffectors their receptors vivo. also highlight discoveries enabled by such tools, revealing molecules signal across timescales learning, orchestrate behavioral changes, modulate circuit activity.

Language: Английский

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The Evolution of Technology‐Driven In Vitro Models for Neurodegenerative Diseases

Advanced Science, Journal Year: 2024, Volume and Issue: 11(16)

Published: Feb. 17, 2024

Abstract The alteration in the neural circuits of both central and peripheral nervous systems is closely related to onset neurodegenerative disorders (NDDs). Despite significant research efforts, knowledge regarding NDD pathological processes, development efficacious drugs are still limited due inability access reproduce components system its intricate microenvironment. 2D culture too simplistic accurately represent more complex dynamic situation cells vivo have therefore been surpassed by 3D systems. However, models suffer from various limitations that can be overcome employing two innovative technologies: organ‐on‐chip printing. In this review, an overview advantages shortcomings microfluidic platforms extracellular matrix‐like biomaterials will given. Then, combination microfluidics hydrogels as a new synergistic approach study analyzing latest advances brain‐on‐chip for explored.

Language: Английский

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Emerging biophysical techniques for probing synaptic transmission in neurodegenerative disorders

Neuroscience, Journal Year: 2024, Volume and Issue: 565, P. 63 - 79

Published: Nov. 26, 2024

Language: Английский

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A network pharmacology approach to identify the mechanisms and molecular targets of curcumin against Alzheimer disease

Medicine, Journal Year: 2022, Volume and Issue: 101(34), P. e30194 - e30194

Published: Aug. 26, 2022

Alzheimer disease (AD) is a degenerative brain disease, which may lead to severe memory loss and other cognitive disorders. However, few effective drugs are available in the clinic at present. Curcumin, major ingredient of traditional Chinese medicine, Curcuma Longa, has various pharmacological activities. Therefore, exploring clinical based on inhibition AD pathological features imperative.First, we utilized HERB database Swisstarget Prediction get related targets curcumin intersected with targets. The intersection were used construct protein-protein interaction network performed gene ontology kyoto encyclopedia genes genomes analyses. Further, obtained against AD-related tau aβ pathology via AlzData database. These applied perform GEO receiver operating characteristic Finally, reliability core was evaluated using molecular docking technology.We identified 49 AD, pathway enrichment analysis demonstrated that (has05010) significantly enriched. Even more, 16 curcumin-related Aβ pathology. Among these targets, 8 involved biological process analyses showed positive regulation cytokine production (GO:0001819) Bioinformatic indicated HMOX1, CSF1R, NFKB1, GSK3B, BACE1, AR, or PTGS1 expression different compared control group patients. studies suggested have good binding force curcumin.In this study, exerted effect treating by regulating multitargets multichannels through method pharmacology.

Language: Английский

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An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 26, 2023

Abstract The serine/threonine kinase AKT is a central node in cell signaling. While aberrant activation underlies the development of variety human diseases, how different patterns AKT-dependent phosphorylation dictate downstream signaling and phenotypic outcomes remains largely enigmatic. Herein, we perform systems-level analysis that integrates methodological advances optogenetics, mass spectrometry-based phosphoproteomics, bioinformatics to elucidate intensity, duration, pattern Akt1 stimulation lead distinct temporal profiles vascular endothelial cells. Through ~35,000 sites across multiple conditions precisely controlled by light stimulation, identify series circuits activated interrogate with growth factor Furthermore, our results categorize substrates are preferably oscillating, transient, sustained signals. We validate list covaried experimental as potential substrates. Our resulting dataset provides rich resource for future studies on dynamics.

Language: Английский

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Multifunctional ultraflexible neural probe for wireless optogenetics and electrophysiology

Giant, Journal Year: 2024, Volume and Issue: 18, P. 100272 - 100272

Published: April 26, 2024

Electrophysiology and optogenetics are pivotal in neuroscience for probing modulating neural activities, playing a vital role unraveling the complexities of brain functionality. Despite their importance, efficacy existing devices is hampered by insufficient functional integration, pronounced foreign body reactions, physical constraints that impede natural animal behaviors. Here, we develop multifunctional, ultraflexible probe designed simultaneous electrophysiological monitoring optical modulation, along with mechanical properties conducive to flexibility compliance. By integrating wireless signal acquisition stimulation circuit, achieved recording signals mice optogenetic control over locomotor behavior. The multifunctional presented this study holds substantial promise closed-loop brain-machine interfaces deepening our understanding circuit functions. This innovative approach addresses aforementioned limitations comprehensive solution vivo interrogation manipulation, marking significant advancement tools available research.

Language: Английский

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Targeting the insular cortex for neuropathic pain modulation: Insights into synaptic and neuronal mechanisms

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(2)

Published: Jan. 20, 2025

Abstract Neuropathic pain, caused by nerve damage, greatly affects quality of life. Recent research proposes modulating brain activity, particularly through electrical stimulation the insular cortex (IC), as a treatment option. This study aimed to understand how IC (ICS) pain modulation. In rat neuropathy model, researchers used optogenetic and ICS techniques evaluate changes in mechanical allodynia synaptic changes, focusing on glutamate receptors (AMPAR, NR2A, NR2B). Optogenetic inhibition neurons relieved without altering plasticity. However, repetitive combined with activation diminished pain‐relieving effects increased AMPAR NR2B receptor levels. Additionally, activating inhibitory also reduced while excitatory lessened effectiveness was associated heightened expression. These findings suggest that inhibiting or could help modulate neuropathic conditions, shedding light can influence management

Language: Английский

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Optogenetic activation of mechanical nociceptions to enhance implant osseointegration

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 31, 2025

Orthopedic implants with high elastic modulus often suffer from poor osseointegration due to stress shielding, a phenomenon that suppresses the expression of intracellular mechanotransduction molecules (IMM) such as focal adhesion kinase (FAK). We find reduced FAK under shielding is also mediated by decreased calcitonin gene-related peptide (CGRP) released Piezo2+ mechanosensitive nerves surrounding implant. To activate these minimally invasively, we develop fully implantable, wirelessly rechargeable optogenetic device. In mice engineered express light-sensitive channels in neurons, targeted stimulation L2-3 dorsal root ganglia (DRG) enhances localized CGRP release near This elevation activates Protein Kinase A (PKA)/FAK signaling pathway bone marrow mesenchymal stem cells (BMSCs), thereby enhancing osteogenesis and improving osseointegration. Here show bioelectronic modulation offers strategy address implant failure, bridging neuroregulation bioengineering. Stress common cause orthopedic reduces activity molecules, which are regulated nociceptors. Here, Wang et al. small, device for regulation nociceptors investigate improve

Language: Английский

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Multi-Frequency Interpolation X-talk Removal Algorithm: Enabling Combinations of Concurrent Optogenetics and Lock-in Amplification Fiber Photometry via Removal of Optogenetic Stimulation Crosstalk

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Simultaneous fiber photometry and optogenetics is a powerful emerging technique for precisely studying the interactions of neuronal brain networks. However, spectral overlap between optogenetic components has severely limited application an all-optical approach. Due to overlap, light from stimulation saturates photosensor occludes fluorescence, which especially problematic in physically smaller model organism brains like mice. Here, we demonstrate multi-frequency interpolation X-talk removal algorithm (MuFIX or μFIX) recovering crosstalk-contaminated responses recorded with lock-in amplification. μFIX exploits multifrequency amplification by modeling remaining uncontaminated data interpolate across crosstalk-affected segments (R2 ≈ 1.0); found that this approach accurately recovers original response after demodulation (Pearson's r 1.0). When applied data, recovered closely resembling dynamics noncrosstalk simultaneously. Upon further verification using simulated empirical demonstrated reproduces any signal underwent crosstalk contamination (r We believe adopting will enable experimental designs simultaneous were previously not feasible due crosstalk.

Language: Английский

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