In Vivo Circuit Analysis

2017 ◽  
Author(s):  
Ryan Bowman ◽  
Hannah Schwennesen ◽  
Kafui Dzirasa ◽  
Rainbo Hultman
Keyword(s):  
Side Effects ◽  
Animal Models ◽  
Psychiatric Disorders ◽  
Neural Circuit ◽  
Brain Regions ◽  
Therapeutic Strategies ◽  
Dynamic Activity ◽  
Wide Range

Breakthroughs in understanding neural circuit activity hold much promise for developing next generation therapeutics for psychiatric disorders. Determination of how dynamic activity is coordinated across brain regions to effect specific behavioral function (or dysfunction) enables the development of therapeutics with increased specificity and fewer side effects. This chapter discusses methodologies for measuring neural circuit activity in humans and in animal models, and describes a bidirectional research pipeline whereby studies in humans are followed by tightly controlled studies in animal models that can then be applied back to humans. Targeted neural circuit manipulations from these studies are already being applied to a wide range of therapeutic strategies.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

scholarly journals Antiartherosclerotic Effects of Plant Flavonoids

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Shamala Salvamani ◽  
Baskaran Gunasekaran ◽  
Noor Azmi Shaharuddin ◽  
Siti Aqlima Ahmad ◽  
Mohd Yunus Shukor
Keyword(s):  
Cardiovascular Diseases ◽  
Side Effects ◽  
Animal Models ◽  
Vascular Diseases ◽  
Lipid Lowering ◽  
Peripheral Vascular ◽  
Heart Attacks ◽  
Synthetic Drug

Atherosclerosis is the process of hardening and narrowing the arteries. Atherosclerosis is generally associated with cardiovascular diseases such as strokes, heart attacks, and peripheral vascular diseases. Since the usage of the synthetic drug, statins, leads to various side effects, the plants flavonoids with antiartherosclerotic activity gained much attention and were proven to reduce the risk of atherosclerosisin vitroandin vivobased on different animal models. The flavonoids compounds also exhibit lipid lowering effects and anti-inflammatory and antiatherogenic properties. The future development of flavonoids-based drugs is believed to provide significant effects on atherosclerosis and its related diseases. This paper discusses the antiatherosclerotic effects of selected plant flavonoids such as quercetin, kaempferol, myricetin, rutin, naringenin, catechin, fisetin, and gossypetin.

scholarly journals Wireless, battery-free optoelectronic systems as subdermal implants for local tissue oximetry

2019 ◽  
Vol 5 (3) ◽  
pp. eaaw0873 ◽  
Author(s):  
Hao Zhang ◽  
Philipp Gutruf ◽  
Kathleen Meacham ◽  
Michael C. Montana ◽  
Xingyue Zhao ◽  
...  
Keyword(s):  
Animal Models ◽  
Tissue Oxygenation ◽  
Human Subjects ◽  
Brain Regions ◽  
Disease States ◽  
Data Output ◽  
Subdermal Implants ◽  
Underlying Mechanisms ◽  
Tissue Oximetry

Monitoring regional tissue oxygenation in animal models and potentially in human subjects can yield insights into the underlying mechanisms of local O2-mediated physiological processes and provide diagnostic and therapeutic guidance for relevant disease states. Existing technologies for tissue oxygenation assessments involve some combination of disadvantages in requirements for physical tethers, anesthetics, and special apparatus, often with confounding effects on the natural behaviors of test subjects. This work introduces an entirely wireless and fully implantable platform incorporating (i) microscale optoelectronics for continuous sensing of local hemoglobin dynamics and (ii) advanced designs in continuous, wireless power delivery and data output for tether-free operation. These features support in vivo, highly localized tissue oximetry at sites of interest, including deep brain regions of mice, on untethered, awake animal models. The results create many opportunities for studying various O2-mediated processes in naturally behaving subjects, with implications in biomedical research and clinical practice.

scholarly journals The Therapeutic Potential of Apigenin

2019 ◽  
Vol 20 (6) ◽  
pp. 1305 ◽  
Author(s):  
Bahare Salehi ◽  
Alessandro Venditti ◽  
Mehdi Sharifi-Rad ◽  
Dorota Kręgiel ◽  
Javad Sharifi-Rad ◽  
...  
Keyword(s):  
Animal Models ◽  
Health Effects ◽  
Therapeutic Potential ◽  
Dietary Assessment ◽  
Functional Activities ◽  
Formulated Diet ◽  
Naturally Occurring ◽  
Wide Range ◽  
Health Promoting

Several plant bioactive compounds have exhibited functional activities that suggest they could play a remarkable role in preventing a wide range of chronic diseases. The largest group of naturally-occurring polyphenols are the flavonoids, including apigenin. The present work is an updated overview of apigenin, focusing on its health-promoting effects/therapeutic functions and, in particular, results of in vivo research. In addition to an introduction to its chemistry, nutraceutical features have also been described. The main key findings from in vivo research, including animal models and human studies, are summarized. The beneficial indications are reported and discussed in detail, including effects in diabetes, amnesia and Alzheimer’s disease, depression and insomnia, cancer, etc. Finally, data on flavonoids from the main public databases are gathered to highlight the apigenin’s key role in dietary assessment and in the evaluation of a formulated diet, to determine exposure and to investigate its health effects in vivo.

In vivo pharmacological characterization of the structurally novel, potent, selective mGlu2/3 receptor agonist LY404039 in animal models of psychiatric disorders

2007 ◽  
Vol 193 (1) ◽  
pp. 121-136 ◽  
Author(s):  
Linda M. Rorick-Kehn ◽  
Bryan G. Johnson ◽  
Karen M. Knitowski ◽  
Craig R. Salhoff ◽  
Jeffrey M. Witkin ◽  
...  
Keyword(s):  
Animal Models ◽  
Psychiatric Disorders ◽  
Receptor Agonist ◽  
Pharmacological Characterization

scholarly journals Longitudinal noninvasive monitoring of transcription factor activation in cardiovascular regulatory nuclei using bioluminescence imaging

2008 ◽  
Vol 33 (2) ◽  
pp. 292-299 ◽  
Author(s):  
Jeffrey R. Peterson ◽  
David W. Infanger ◽  
Valdir A. Braga ◽  
Yulong Zhang ◽  
Ram V. Sharma ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gene Transfer ◽  
Molecular Mechanisms ◽  
Bioluminescence Imaging ◽  
Brain Regions ◽  
Luciferase Reporter ◽  
Viral Gene ◽  
Adenoviral Delivery ◽  
Wide Range

The ability to monitor transcription factor (TF) activation in the central nervous system (CNS) has the potential to provide novel information regarding the molecular mechanisms underlying a wide range of neurobiological processes. However, traditional biochemical assays limit the mapping of TF activity to select time points. In vivo bioluminescence imaging (BLI) has emerged as an attractive technology for visualizing internal molecular events in the same animal over time. Here, we evaluated the utility of BLI, in combination with virally mediated delivery of reporter constructs to cardiovascular nuclei, for monitoring of TF activity in these discrete brain regions. Following viral gene transfer of NF-κB-driven luciferase reporter to the subfornical organ (SFO), BLI enabled daily measurements of baseline TF activity in the same animal for 1 mo. Importantly, systemic endotoxin, a stimulator of NF-κB activity, induced dramatic and dose-dependent increases in NF-κB-dependent bioluminescence in the SFO up to 30 days after gene transfer. Cotreatment with a dominant-negative IκBα mutant significantly prevented endotoxin-dependent NF-κB activation, confirming the specificity of the bioluminescence signal. NF-κB-dependent luminescence signals were also stable and inducible 1 mo following delivery of luciferase reporter construct to the paraventricular nucleus or rostral ventrolateral medulla. Lastly, using targeted adenoviral delivery of an AP-1 responsive luciferase reporter, we showed similar baseline and endotoxin-induced AP-1 activity in these same brain regions as with NF-κB reporters. These results demonstrate that BLI, in combination with virally mediated gene transfer, is a powerful method for longitudinal monitoring and quantification of TF activity in targeted CNS nuclei in vivo.

scholarly journals Synaptic plasticity in the mesolimbic dopamine system

2003 ◽  
Vol 358 (1432) ◽  
pp. 815-819 ◽  
Author(s):  
Mark J. Thomas ◽  
Robert C. Malenka
Keyword(s):  
Synaptic Plasticity ◽  
Drugs Of Abuse ◽  
Neural Circuit ◽  
Long Term Potentiation ◽  
Brain Regions ◽  
Mesolimbic Dopamine ◽  
Dopamine System ◽  
Mesolimbic Dopamine System

Long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical mechanisms that contribute to the neural circuit modifications that mediate all forms of experience-dependent plasticity. It has, however, been difficult to demonstrate directly that experience causes long-lasting changes in synaptic strength and that these mediate changes in behaviour. To address these potential functional roles of LTP and LTD, we have taken advantage of the powerful in vivo effects of drugs of abuse that exert their behavioural effects in large part by acting in the nucleus accumbens (NAc) and ventral tegmental area (VTA); the two major components of the mesolimbic dopamine system. Our studies suggest that in vivo drugs of abuse such as cocaine cause long-lasting changes at excitatory synapses in the NAc and VTA owing to activation of the mechanisms that underlie LTP and LTD in these structures. Thus, administration of drugs of abuse provides a distinctive model for further investigating the mechanisms and functions of synaptic plasticity in brain regions that play important roles in the control of motivated behaviour, and one with considerable practical implications.

scholarly journals Chemical and biological assessment of metal organic frameworks (MOFs) in pulmonary cells and in an acute in vivo model: relevance to pulmonary arterial hypertension therapy

2017 ◽  
Vol 7 (3) ◽  
pp. 643-653 ◽  
Author(s):  
Nura A. Mohamed ◽  
Robert P. Davies ◽  
Paul D. Lickiss ◽  
Blerina Ahmetaj-Shala ◽  
Daniel M. Reed ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Side Effects ◽  
Arterial Hypertension ◽  
Therapeutic Window ◽  
Endothelin 1 ◽  
Wide Range ◽  
Metal Organic ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a progressive and debilitating condition. Despite promoting vasodilation, current drugs have a therapeutic window within which they are limited by systemic side effects. Nanomedicine uses nanoparticles to improve drug delivery and/or reduce side effects. We hypothesize that this approach could be used to deliver PAH drugs avoiding the systemic circulation. Here we report the use of iron metal organic framework (MOF) MIL-89 and PEGylated MIL-89 (MIL-89 PEG) as suitable carriers for PAH drugs. We assessed their effects on viability and inflammatory responses in a wide range of lung cells including endothelial cells grown from blood of donors with/without PAH. Both MOFs conformed to the predicted structures with MIL-89 PEG being more stable at room temperature. At concentrations up to 10 or 30 µg/mL, toxicity was only seen in pulmonary artery smooth muscle cells where both MOFs reduced cell viability and CXCL8 release. In endothelial cells from both control donors and PAH patients, both preparations inhibited the release of CXCL8 and endothelin-1 and in macrophages inhibited inducible nitric oxide synthase activity. Finally, MIL-89 was well-tolerated and accumulated in the rat lungs when given in vivo. Thus, the prototypes MIL-89 and MIL-89 PEG with core capacity suitable to accommodate PAH drugs are relatively non-toxic and may have the added advantage of being anti-inflammatory and reducing the release of endothelin-1. These data are consistent with the idea that these materials may not only be useful as drug carriers in PAH but also offer some therapeutic benefit in their own right.

scholarly journals Scaling of optogenetically evoked signaling in a higher-order corticocortical pathway in the anesthetized mouse

2017 ◽  
Author(s):  
Xiaojian Li ◽  
Naoki Yamawaki ◽  
John M. Barrett ◽  
Konrad P. Körding ◽  
Gordon M. G. Shepherd
Keyword(s):  
Motor Cortex ◽  
Higher Order ◽  
Retrosplenial Cortex ◽  
Complex Activity ◽  
Dynamic Activity ◽  
Sensory Stimuli ◽  
Awake State ◽  
Wide Range ◽  
Stimulus Parameters

ABSTRACTQuantitative analysis of corticocortical signaling is needed to understand and model information processing in cerebral networks. However, higher-order pathways, hodologically remote from sensory input, are not amenable to spatiotemporally precise activation by sensory stimuli. Here, we combined parametric channelrhodopsin-2 (ChR2) photostimulation with multi-unit electrophysiology to study corticocortical driving in a parietofrontal pathway from retrosplenial cortex (RSC) to posterior secondary motor cortex (M2) in mice in vivo. Ketamine anesthesia was used both to eliminate complex activity associated with the awake state and to enable stable recordings of responses over a wide range of stimulus parameters. Photostimulation of ChR2-expressing neurons in RSC, the upstream area, produced local activity that decayed quickly. This activity in turn drove downstream activity in M2 that arrived rapidly (5-10 ms latencies), and scaled in amplitude across a wide range of stimulus parameters as an approximately constant fraction (~0.2) of the upstream activity. A model-based analysis could explain the corticocortically driven activity with exponentially decaying kernels (~20 ms time constant) and small delay. Reverse (antidromic) driving was similarly robust. The results show that corticocortical signaling in this pathway drives downstream activity rapidly and scalably, in a mostly linear manner. These properties, identified in anesthetized mice and represented in a simple model, suggest a robust basis for supporting complex non-linear dynamic activity in corticocortical circuits in the awake state.SIGNIFICANCE STATEMENTThe signaling properties of corticocortical connections are not well understood, particularly for higher-order inter-areal pathways. Here, we developed a paradigm based on parametric optogenetic photostimulation, linear-array electrophysiology, and mathematical modeling to characterize signaling along corticortical connections linking retrosplenial cortex to posterior secondary motor cortex (M2) in anesthetized mice. The results indicate that corticocortically driven activity in the downstream area followed the optogenetically evoked upstream activity in a rapid and scalable manner, and could be described with a simple linear integrator model. These findings suggest that this pathway, when activated selectively in the unconscious state, supports intrinsically linear inter-areal communication.

scholarly journals A data-driven approach to the automated mapping of functional brain topographies across species

2018 ◽  
Author(s):  
Wolfgang M. Pauli
Keyword(s):  
Animal Models ◽  
Psychiatric Disorders ◽  
Large Scale ◽  
Brain Regions ◽  
Behavioral Neuroscience ◽  
Open Questions ◽  
Dorsolateral Prefrontal ◽  
Neuroimaging Data ◽  
Data Driven Approach ◽  
Species Mapping

AbstractBehavioral neuroscience has made great strides in developing animal models of human behavior and psychiatric disorders. Animal models allow for the formulation of hypotheses regarding the mechanisms underlying psychiatric disorders, and the opportunity to test these hypotheses using procedures that are too invasive for human participants. However, recent scientific reviews have highlighted the low success rate of translating results from animal models into clinical interventions in humans. A potential roadblock is that bidirectional functional mappings between the human and rodent brain are incomplete. To narrow this gap, we created a framework, Neurobabel, for performing large-scale automated synthesis of human neuroimaging data and behavioral neuroscience data. By leveraging the semantics of how researchers within each field describe their studies, this framework enables region to region mapping of brain regions across species, as well as cross-species mapping of psychological functions. As a proof of concept, we utilize the framework to create a functional cross-species mapping between the amygdala and hippocampus for fear-related and spatial memories, respectively. We then proceed to address two open questions in the field: (1) Do rodents have a dorsolateral prefrontal cortex? (2) Which human brain region corresponds to the rodent prelimbic cortex?

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