scholarly journals Development of optically controlled “living electrodes” with long-projecting axon tracts for a synaptic brain-machine interface

2021 ◽  
Vol 7 (4) ◽  
pp. eaay5347
Author(s):  
Dayo O. Adewole ◽  
Laura A. Struzyna ◽  
Justin C. Burrell ◽  
James P. Harris ◽  
Ashley D. Nemes ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Brain Activity ◽  
Optical Recording ◽  
New Class ◽  
Brain Surface ◽  
Machine Interface ◽  
The Brain

For implantable neural interfaces, functional/clinical outcomes are challenged by limitations in specificity and stability of inorganic microelectrodes. A biological intermediary between microelectrical devices and the brain may improve specificity and longevity through (i) natural synaptic integration with deep neural circuitry, (ii) accessibility on the brain surface, and (iii) optogenetic manipulation for targeted, light-based readout/control. Accordingly, we have developed implantable “living electrodes,” living cortical neurons, and axonal tracts protected within soft hydrogel cylinders, for optobiological monitoring/modulation of brain activity. Here, we demonstrate fabrication, rapid axonal outgrowth, reproducible cytoarchitecture, and simultaneous optical stimulation and recording of these tissue engineered constructs in vitro. We also present their transplantation, survival, integration, and optical recording in rat cortex as an in vivo proof of concept for this neural interface paradigm. The creation and characterization of these functional, optically controllable living electrodes are critical steps in developing a new class of optobiological tools for neural interfacing.

scholarly journals Development of Optically-Controlled “Living Electrodes” with Long-Projecting Axon Tracts for a Synaptic Brain-Machine Interface

2018 ◽  
Author(s):  
Dayo O. Adewole ◽  
Laura A. Struzyna ◽  
James P. Harris ◽  
Ashley D. Nemes ◽  
Justin C. Burrell ◽  
...  
Keyword(s):  
Brain Activity ◽  
Optical Recording ◽  
Neural Interfaces ◽  
New Class ◽  
Brain Surface ◽  
Long Term Performance ◽  
Term Performance ◽  
The Brain

AbstractAchievements in intracortical neural interfaces are compromised by limitations in specificity and long-term performance. A biological intermediary between devices and the brain may offer improved specificity and longevity through natural synaptic integration with deep neural circuitry, while being accessible on the brain surface for optical read-out/control. Accordingly, we have developed the first “living electrodes” comprised of implantable axonal tracts protected within soft hydrogel cylinders for the biologically-mediated monitoring/modulation of brain activity. Here we demonstrate the controlled fabrication, rapid axonal outgrowth, reproducible cytoarchitecture, and simultaneous optical stimulation and recording of neuronal activity within these engineered constructs in vitro. We also present their transplantation, survival, integration, and optical recording in rat cortex in vivo as a proof-of-concept for this neural interface paradigm. The creation and functional validation of these preformed, axon-based “living electrodes” is a critical step towards developing a new class of biohybrid neural interfaces to probe and modulate native circuitry.

scholarly journals Modulator of apoptosis-1 is a potential therapeutic target in acute ischemic injury

2018 ◽  
Vol 39 (12) ◽  
pp. 2406-2418 ◽  
Author(s):  
Su Jing Chan ◽  
Hui Zhao ◽  
Kazuhide Hayakawa ◽  
Chou Chai ◽  
Chong Teik Tan ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Infarct Volume ◽  
Neuronal Loss ◽  
Ischemic Injury ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
In Vivo Models ◽  
The Brain

Modulator of apoptosis 1 (MOAP-1) is a Bax-associating protein highly enriched in the brain. In this study, we examined the role of MOAP-1 in promoting ischemic injuries following a stroke by investigating the consequences of MOAP-1 overexpression or deficiency in in vitro and in vivo models of ischemic stroke. MOAP-1 overexpressing SH-SY5Y cells showed significantly lower cell viability following oxygen and glucose deprivation (OGD) treatment when compared to control cells. Consistently, MOAP-1−/− primary cortical neurons were observed to be more resistant against OGD treatment than the MOAP-1+/+ primary neurons. In the mouse transient middle cerebral artery occlusion (tMCAO) model, ischemia triggered MOAP-1/Bax association, suggested activation of the MOAP-1-dependent apoptotic cascade. MOAP-1−/− mice were found to exhibit reduced neuronal loss and smaller infarct volume 24 h after tMCAO when compared to MOAP-1+/+ mice. Correspondingly, MOAP-1−/− mice also showed better integrity of neurological functions as demonstrated by their performance in the rotarod test. Therefore, both in vitro and in vivo data presented strongly support the conclusion that MOAP-1 is an important apoptotic modulator in ischemic injury. These results may suggest that a reduction of MOAP-1 function in the brain could be a potential therapeutic approach in the treatment of acute stroke.

scholarly journals Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1-40) Fibrils

2018 ◽  
Author(s):  
Francesco Tavanti ◽  
Alfonso Pedone ◽  
Maria Cristina Menziani
Keyword(s):  
Therapeutic Strategy ◽  
Therapeutic Potential ◽  
Structure Stability ◽  
Insoluble Form ◽  
The Brain ◽  
Identification And Characterization ◽  
Insight Into

One of the principal hallmarks of Alzheimer’s disease (AD) is related to the aggregation of amyloid-β fibrils in an insoluble form in the brain, also known as amyloidosis. Therefore, a prominent therapeutic strategy against AD consists either in blocking the amyloid aggregation and/or destroying the already formed aggregates. Natural products have shown significant therapeutic potential as amyloid inhibitors from in vitro studies as well as in vivo animal tests. In this study, the interaction of five natural biophenols (curcumin, dopamine, (-)-Epigallocatechin-3-gallate, Quercetin, and Rosmarinic acid) with the amyloid-β(1-40) fibrils has been studied through computational simulations. The results allowed the identification and characterization of the different binding modalities of each compounds and their consequences on fibril dynamics and aggregation. It emerges that the lateral aggregation of the fibrils is strongly influenced by the intercalation of the ligands, which modulate the double-layered structure stability.

Fabrication and Characterization of Biodegradable Metal Based Microelectrodes for In Vivo Neural Recording

MRS Advances ◽  
2019 ◽  
Vol 4 (46-47) ◽  
pp. 2471-2477
Author(s):  
Chaoxing Zhang ◽  
Teresa H. Wen ◽  
Khaleel A. Razak ◽  
Jiajia Lin ◽  
Edgar Villafana ◽  
...  
Keyword(s):  
Neural Recording ◽  
Neural Signals ◽  
Secondary Surgery ◽  
New Class ◽  
Fabrication And Characterization ◽  
Evoked Activity ◽  
First Time ◽  
The Brain

ABSTRACT:Neural electrodes have been widely used to monitor neural signals and/or deliver electrical stimulation in the brain. Currently, biodegradable and biocompatible materials have been actively investigated to create temporary electrodes that could degrade after serving their functions for neural recording and stimulation from days to months. The new class of biodegradable electrodes eliminate the necessity of secondary surgery for electrode removal. In this study, we created biodegradable, biocompatible, and implantable magnesium (Mg)-based microelectrodes for in vivo neural recording for the first time. Specifically, conductive poly-3,4-ethylenedioxythiophene (PEDOT) was first deposited onto Mg microwire substrates by electrochemical deposition, and a biodegradable insulating polymer was subsequently sprayed onto the surface of electrodes. The tip of electrodes was designed to be conductive for neural recording and stimulation, while the rest of electrodes was insulated with a polymer that is biocompatible with neural tissue. The impedance of Mg-based microelectrodes and their performance during neural recording in the auditory cortex of a mouse were studied. The results first demonstrated the capability of Mg-based microelectrodes for in vivo recording of multi-unit stimulus-evoked activity in the brain.

scholarly journals Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus

2014 ◽  
Vol 95 (5) ◽  
pp. 1025-1032 ◽  
Author(s):  
Daniel L. Horton ◽  
Ashley C. Banyard ◽  
Denise A. Marston ◽  
Emma Wise ◽  
David Selden ◽  
...  
Keyword(s):  
Laboratory Mouse ◽  
Rabies Vaccine ◽  
Molecular Techniques ◽  
Phenotypic Characteristics ◽  
Nucleotide Divergence ◽  
The Brain

In 2009, a novel lyssavirus (subsequently named Ikoma lyssavirus, IKOV) was detected in the brain of an African civet (Civettictis civetta) with clinical rabies in the Serengeti National Park of Tanzania. The degree of nucleotide divergence between the genome of IKOV and those of other lyssaviruses predicted antigenic distinction from, and lack of protection provided by, available rabies vaccines. In addition, the index case was considered likely to be an incidental spillover event, and therefore the true reservoir of IKOV remained to be identified. The advent of sensitive molecular techniques has led to a rapid increase in the discovery of novel viruses. Detecting viral sequence alone, however, only allows for prediction of phenotypic characteristics and not their measurement. In the present study we describe the in vitro and in vivo characterization of IKOV, demonstrating that it is (1) pathogenic by peripheral inoculation in an animal model, (2) antigenically distinct from current rabies vaccine strains and (3) poorly neutralized by sera from humans and animals immunized against rabies. In a laboratory mouse model, no protection was elicited by a licensed rabies vaccine. We also investigated the role of bats as reservoirs of IKOV. We found no evidence for infection among 483 individuals of at least 13 bat species sampled across sites in the Serengeti and Southern Kenya.

scholarly journals A chloroquine-resistant Swiss 3T3 cell line with a defect in late endocytic acidification

1988 ◽  
Vol 106 (2) ◽  
pp. 269-277 ◽  
Author(s):  
CC Cain ◽  
RF Murphy
Keyword(s):  
Acridine Orange ◽  
Cell Line ◽  
Second Phase ◽  
Lysosomal Fraction ◽  
New Class ◽  
Swiss 3T3 Cell

To investigate the role of acidification in cell proliferation, several cell lines resistant to chloroquine were isolated with the expectation that some would express altered endocytic acidification. The preliminary characterization of one of these lines, CHL60-64, is described. In contrast to endocytic mutants described previously, the initial phase of endocytic acidification, as measured by transferrin acidification, is normal in this cell line. However, a difference in subsequent endocytic acidification was observed in CHL60-64. In the parental cells, internalized dextran was fully acidified to approximately pH 5.5 within 1 h. In CHL60-64, the pH in the endocytic compartment was only 6.1 after 1 h and remained as high as 5.8 for at least 4 h. After an 8-h incubation, the pH decreased to 5.5, indicating that the second phase of acidification is only slowed in CHL60-64, and not blocked. Consistent with this retarded acidification, ATP-dependent acidification in vitro (as measured by acridine orange accumulation) was reduced in both the lysosomal fraction and the endosomal fraction isolated from CHL60-64. A decrease in the in vivo rate of acridine orange accumulation after perturbation with amine was also observed. In addition to amine resistance and defective acidification, CHL60-64 was found to be resistant to vacuolation in the presence of chloroquine and ammonium chloride, and was resistant to ouabain. Further studies on this new class of endocytosis mutant, in combination with existing mutants, should help to clarify the mechanisms responsible for the regulation of endocytic acidification.

scholarly journals Identification and characterization of influenza variants resistant to a viral endonuclease inhibitor

2016 ◽  
Vol 113 (13) ◽  
pp. 3669-3674 ◽  
Author(s):  
Min-Suk Song ◽  
Gyanendra Kumar ◽  
William R. Shadrick ◽  
Wei Zhou ◽  
Trushar Jeevan ◽  
...  
Keyword(s):  
Point Mutations ◽  
Random Mutagenesis ◽  
Resistant Mutant ◽  
Inhibitor Binding ◽  
New Class ◽  
Identification And Characterization ◽  
Modest Reduction

The influenza endonuclease is an essential subdomain of the viral RNA polymerase. It processes host pre-mRNAs to serve as primers for viral mRNA and is an attractive target for antiinfluenza drug discovery. Compound L-742,001 is a prototypical endonuclease inhibitor, and we found that repeated passaging of influenza virus in the presence of this drug did not lead to the development of resistant mutant strains. Reduced sensitivity to L-742,001 could only be induced by creating point mutations via a random mutagenesis strategy. These mutations mapped to the endonuclease active site where they can directly impact inhibitor binding. Engineered viruses containing the mutations showed resistance to L-742,001 both in vitro and in vivo, with only a modest reduction in fitness. Introduction of the mutations into a second virus also increased its resistance to the inhibitor. Using the isolated wild-type and mutant endonuclease domains, we used kinetics, inhibitor binding and crystallography to characterize how the two most significant mutations elicit resistance to L-742,001. These studies lay the foundation for the development of a new class of influenza therapeutics with reduced potential for the development of clinical endonuclease inhibitor-resistant influenza strains.

scholarly journals Depletion of Intracellular Zinc from Neurons by Use of an Extracellular Chelator In Vivo and In Vitro

2002 ◽  
Vol 50 (12) ◽  
pp. 1659-1662 ◽  
Author(s):  
Christopher J. Frederickson ◽  
Sang W. Suh ◽  
Jae-Young Koh ◽  
Yoo K. Cha ◽  
Richard B. Thompson ◽  
...  
Keyword(s):  
General Result ◽  
Cortical Neurons ◽  
Zinc Ion ◽  
Purkinje Neurons ◽  
Intracellular Zinc ◽  
Ion Efflux ◽  
Intracellular Compartments ◽  
The Brain

The membrane-impermeable chelator CaEDTA was introduced extracellularly among neurons in vivo and in vitro for the purpose of chelating extracellular Zn2+. Unexpectedly, this treatment caused histochemically reactive Zn2+ in intracellular compartments to drop rapidly. The same general result was seen with intravesicular Zn2+, which fell after CaEDTA infusion into the lateral ventricle of the brain, with perikaryal Zn2+ in Purkinje neurons (in vivo) and with cortical neurons (in vitro). These findings suggest either that the volume of zinc ion efflux and reuptake is higher than previously suspected or that EDTA can enter cells and vesicles. Caution is therefore warranted in attempting to manipulate extracellular or intracellular Zn2+ selectively.

Localization and characterization of cytochrome P450 in the brain. In vivo and in vitro investigations on phenytoin- and phenobarbital-inducible isoforms

1995 ◽  
Vol 82-83 ◽  
pp. 655-662 ◽  
Author(s):  
Benedikt Volk ◽  
Ralf P. Meyer ◽  
Friederike von Lintig ◽  
Bernd Ibach ◽  
Rolf Knoth
Keyword(s):  
Cytochrome P450 ◽  
The Brain

scholarly journals Discovery and characterization of a fourth class of guanidine riboswitches

2020 ◽  
Vol 48 (22) ◽  
pp. 12889-12899
Author(s):  
Felina Lenkeit ◽  
Iris Eckert ◽  
Jörg S Hartig ◽  
Zasha Weinberg
Keyword(s):  
Biological Significance ◽  
Protein Domains ◽  
Structural Class ◽  
New Class ◽  
In Vivo Experiments ◽  
Fourth Class ◽  
Metabolite Binding

Abstract Riboswitches are RNAs that specifically sense a small molecule and regulate genes accordingly. The recent discovery of guanidine-binding riboswitches revealed the biological significance of this compound, and uncovered genes related to its biology. For example, certain sugE genes encode guanidine exporters and are activated by the riboswitches to reduce toxic levels of guanidine in the cell. In order to study guanidine biology and riboswitches, we applied a bioinformatics strategy for discovering additional guanidine riboswitches by searching for new candidate motifs associated with sugE genes. Based on in vitro and in vivo experiments, we determined that one of our six best candidates is a new structural class of guanidine riboswitches. The expression of a genetic reporter was induced 80-fold in response to addition of 5 mM guanidine in Staphylococcus aureus. This new class, called the guanidine-IV riboswitch, reveals additional guanidine-associated protein domains that are extremely rarely or never associated with previously established guanidine riboswitches. Among these protein domains are two transporter families that are structurally distinct from SugE, and could represent novel types of guanidine exporters. These results establish a new metabolite-binding RNA, further validate a bioinformatics method for finding riboswitches and suggest substrate specificities for as-yet uncharacterized transporter proteins.

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