Linking Ethanol-Addictive Behaviors With Brain Catecholamines: Release Pattern Matters

Using a variety of animal models that simulate key features of the alcohol use disorder (AUD), remarkable progress has been made in identifying neurochemical targets that may contribute to the development of alcohol addiction. In this search, the dopamine (DA) and norepinephrine (NE) systems have been long thought to play a leading role in comparison with other brain systems. However, just recent development and application of optogenetic approaches into the alcohol research field provided opportunity to identify neuronal circuits and specific patterns of neurotransmission that govern the key components of ethanol-addictive behaviors. This critical review summarizes earlier findings, which initially disclosed catecholamine substrates of ethanol actions in the brain and shows how the latest methodologies help us to reveal the significance of DA and NE release changes. Specifically, we focused on recent optogenetic investigations aimed to reveal cause-effect relationships between ethanol-drinking (seeking and taking) behaviors and catecholamine dynamics in distinct brain pathways. These studies gain the knowledge that is needed for the better understanding addiction mechanisms and, therefore, for development of more effective AUD treatments. Based on the reviewed findings, new messages for researches were indicated, which may have broad applications beyond the field of alcohol addiction.

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3. Through the looking glass

Telescopes: A Very Short Introduction ◽

10.1093/actrade/9780198745860.003.0003 ◽

2016 ◽

pp. 19-38

Author(s):

Geoff Cottrell

Keyword(s):

17Th Century ◽

16Th Century ◽

Leading Role ◽

Key Features ◽

Cassegrain Telescope ◽

Glass Lenses ◽

Looking Glass ◽

Made In

The magnifying property of glass lenses has been known about since antiquity, but telescopes were first made in the 16th century, and in the early 17th century Galileo created a telescope powerful enough to see stars sixty-four times fainter than with unaided eyes. ‘Through the looking glass’ outlines the key features of the two main types of telescopes: reflectors and refractors. In order to see deeper into our cosmos, bigger and bigger telescopes have been needed. Three great reflector telescopes are described: George Hale’s 60-inch (1.5 m) Cassegrain Telescope from 1908, the 100-inch Hooker Telescope from 1917, and the 200-inch Hale Telescope that has played a leading role in astronomy and cosmology for at least three decades.

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Animal models of alcohol use disorder and the brain: From casual drinking to dependence.

Translational Issues in Psychological Science ◽

10.1037/tps0000198 ◽

2019 ◽

Vol 5 (3) ◽

pp. 222-242 ◽

Cited By ~ 3

Author(s):

Nicole A. Crowley ◽

Nigel C. Dao ◽

Sarah N. Magee ◽

Alexandre J. Bourcier ◽

Emily G. Lowery-Gionta

Keyword(s):

Alcohol Use ◽

Animal Models ◽

Alcohol Use Disorder ◽

The Brain

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Soil and ecological division into districts of the Baikal region

Geodesy and Cartography ◽

10.22389/0016-7126-2018-940-10-54-64 ◽

2018 ◽

Vol 940 (10) ◽

pp. 54-64 ◽

Cited By ~ 1

Author(s):

I.A. Belozertseva ◽

A.A. Sorokovoj

Keyword(s):

Baikal Region ◽

Soil Cover ◽

Soil Formation ◽

Forest Steppe ◽

Leading Role ◽

Soil Cover Structure ◽

Reflecting Surface ◽

Heat And Moisture ◽

Made In

On the basis of long-term researches of soils in the territory of Russia and Mongolia soil and ecological division into districts of the Baikal region is carried out. At division into districts the whole set of an environment of soil formation was considered. On the map of soil and ecological division into districts 13 mountain, mid-mountain, low-mountain taiga, foothill, hollow-valley, forest-steppe and steppe provinces reflecting surface device originality as the ratio of balance of heat and moisture forming a basis to zoning is shown against the background of difficult orography are allocated. In total 42 districts on lithologic-geomorphological features are allocated. In formation of distinctions of a soil cover of these provinces the leading role is played by bioclimatic factors and inside them the lithologic-geomorphological ones. In the view of structural approach of the district they are considered as territories with a certain natural change of several types of the soil cover structure caused by features of a relief and the parent rock. The map is made in the MapInfo program. It is revealed that on ill-defined width zoning of soils the vertical one which has a greater influence on soils of this region is imposed. Soils of the Baikal region are not similar to the soils located at the same latitude of the flat European territory of Russia. Zone soils of this territory are specific and original.

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Alcohol Use Disorder

10.1093/oso/9780190676001.003.0005 ◽

2018 ◽

Author(s):

Igor Ponomarev

Keyword(s):

Alcohol Use ◽

Alcohol Use Disorder ◽

Critical Discussion ◽

Epigenetic Mechanisms ◽

Future Directions ◽

Clinically Significant ◽

Early Life Exposures ◽

The Brain ◽

Epigenetic Research

Alcohol use disorder (AUD) is characterized by clinically significant impairments in health and social function. Epigenetic mechanisms of gene regulation may provide an attractive explanation for how early life exposures to alcohol contribute to the development of AUD and exert lifelong effects on the brain. This chapter provides a critical discussion of the role of epigenetic mechanisms in AUD etiology and the potential of epigenetic research to improve diagnosis, evaluate risks for alcohol-induced pathologies, and promote development of novel therapies for the prevention and treatment of AUD. Challenges of the current epigenetic approaches and future directions are also discussed.

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Diagnosis and Therapeutic Management of Liver Fibrosis by microRNA

International Journal of Molecular Sciences ◽

10.3390/ijms22158139 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8139

Author(s):

Tomoko Tadokoro ◽

Asahiro Morishita ◽

Tsutomu Masaki

Keyword(s):

Liver Fibrosis ◽

Viral Infections ◽

Primary Biliary Cholangitis ◽

Medical Need ◽

Key Factor ◽

Complications Of Cirrhosis ◽

And Control ◽

Functional Rnas ◽

Remarkable Progress ◽

Made In

Remarkable progress has been made in the treatment and control of hepatitis B and C viral infections. However, fundamental treatments for diseases in which liver fibrosis is a key factor, such as cirrhosis, alcoholic/nonalcoholic steatohepatitis, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, are still under development and remain an unmet medical need. To solve this problem, it is essential to elucidate the pathogenesis of liver fibrosis in detail from a molecular and cellular perspective and to develop targeted therapeutic agents based on this information. Recently, microRNAs (miRNAs), functional RNAs of 22 nucleotides, have been shown to be involved in the pathogenesis of liver fibrosis. In addition, extracellular vesicles called “exosomes” have been attracting attention, and research is being conducted to establish noninvasive and extremely sensitive biomarkers using miRNAs in exosomes. In this review, we summarize miRNAs directly involved in liver fibrosis, miRNAs associated with diseases leading to liver fibrosis, and miRNAs related to complications of cirrhosis. We will also discuss the efficacy of each miRNA as a biomarker of liver fibrosis and pathology, and its potential application as a therapeutic agent.

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Molecular Mechanisms of Drug Resistance in Glioblastoma

International Journal of Molecular Sciences ◽

10.3390/ijms22126385 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6385

Author(s):

Maya A. Dymova ◽

Elena V. Kuligina ◽

Vladimir A. Richter

Keyword(s):

Drug Resistance ◽

Brain Tumor ◽

Molecular Mechanisms ◽

Primary Brain Tumor ◽

Therapeutic Resistance ◽

Molecular Characteristics ◽

Blood Brain ◽

Conventional Radiation ◽

The Brain ◽

Made In

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).

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Implantable Thin Film Devices as Brain-Computer Interfaces: Recent Advances in Design and Fabrication Approaches

Coatings ◽

10.3390/coatings11020204 ◽

2021 ◽

Vol 11 (2) ◽

pp. 204

Author(s):

Yuhao Zhou ◽

Bowen Ji ◽

Minghao Wang ◽

Kai Zhang ◽

Shuaiqi Huangfu ◽

...

Keyword(s):

Thin Film ◽

High Resolution ◽

Future Research ◽

Nano Fabrication ◽

Computer Interfaces ◽

Continuous Progress ◽

Open Mesh ◽

Remarkable Progress ◽

Thin Film Devices ◽

Made In

Remarkable progress has been made in the high resolution, biocompatibility, durability and stretchability for the implantable brain-computer interface (BCI) in the last decades. Due to the inevitable damage of brain tissue caused by traditional rigid devices, the thin film devices are developing rapidly and attracting considerable attention, with continuous progress in flexible materials and non-silicon micro/nano fabrication methods. Therefore, it is necessary to systematically summarize the recent development of implantable thin film devices for acquiring brain information. This brief review subdivides the flexible thin film devices into the following four categories: planar, open-mesh, probe, and micro-wire layouts. In addition, an overview of the fabrication approaches is also presented. Traditional lithography and state-of-the-art processing methods are discussed for the key issue of high-resolution. Special substrates and interconnects are also highlighted with varied materials and fabrication routines. In conclusion, a discussion of the remaining obstacles and directions for future research is provided.

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Ibudilast, a neuroimmune modulator, reduces heavy drinking and alcohol cue-elicited neural activation: a randomized trial

Translational Psychiatry ◽

10.1038/s41398-021-01478-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Erica N. Grodin ◽

Spencer Bujarski ◽

Brandon Towns ◽

Elizabeth Burnette ◽

Steven Nieto ◽

...

Keyword(s):

Macrophage Migration Inhibitory Factor ◽

Alcohol Use Disorder ◽

Cue Reactivity ◽

Negative Mood ◽

Heavy Drinking ◽

Neural Activation ◽

Daily Diary Study ◽

Alcohol Cues ◽

To Receive ◽

The Brain

AbstractIbudilast, a neuroimmune modulator which selectively inhibits phosphodiesterases (PDE)-3, -4, -10, and -11, and macrophage migration inhibitory factor (MIF), shows promise as a novel pharmacotherapy for alcohol use disorder (AUD). However, the mechanisms of action underlying ibudilast’s effects on the human brain remain largely unknown. Thus, the current study examined the efficacy of ibudilast to improve negative mood, reduce heavy drinking, and attenuate neural reward signals in individuals with AUD. Fifty-two nontreatment-seeking individuals with AUD were randomized to receive ibudilast (n = 24) or placebo (n = 28). Participants completed a 2-week daily diary study during which they filled out daily reports of their past day drinking, mood, and craving. Participants completed an functional magnetic resonance imaging (fMRI) alcohol cue-reactivity paradigm half-way through the study. Ibudilast did not have a significant effect on negative mood (β = −0.34, p = 0.62). However, ibudilast, relative to placebo, reduced the odds of heavy drinking across time by 45% (OR = 0.55, (95% CI: 0.30, 0.98)). Ibudilast also attenuated alcohol cue-elicited activation in the ventral striatum (VS) compared to placebo (F(1,44) = 7.36, p = 0.01). Alcohol cue-elicited activation in the VS predicted subsequent drinking in the ibudilast group (F(1,44) = 6.39, p = 0.02), such that individuals who had attenuated ventral striatal activation and took ibudilast had the fewest number of drinks per drinking day in the week following the scan. These findings extend preclinical and human laboratory studies of the utility of ibudilast to treat AUD and suggest a biobehavioral mechanism through which ibudilast acts, namely, by reducing the rewarding response to alcohol cues in the brain leading to a reduction in heavy drinking.

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Smooth Muscle Contraction: Recent Advances

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y94-189 ◽

1994 ◽

Vol 72 (11) ◽

pp. 1317-1319

Author(s):

Newman L. Stephens

Keyword(s):

Smooth Muscle ◽

Muscle Contraction ◽

Myosin Light Chain ◽

Kinase Activity ◽

Smooth Muscle Contraction ◽

Recent Advances ◽

Regulation Of Contraction ◽

Muscle Biochemistry ◽

Remarkable Progress ◽

Made In

Research in smooth muscle contraction has shown remarkable progress over the last 5 years. Striking advances have been made in the areas of biochemical regulation of contraction, centering on myosin light chain kinase activity, and of biophysical delineation of the contractile process at the actomyosin level by use of the newly developed motility assay. The purpose of the symposium held at Minaki, Ont., was to obtain a comprehensive reporting of the recent advances made in the area of smooth muscle contraction. Specifically, advances in the areas of biophysics of contraction, energetics, and contractile and regulator proteins (including the interesting newcomers caldesmon and calponin) and the changes that occur in pathophysiological entities such as asthma, hypertension, anaphylactic shock, high-altitude hypoxia, and persistent pulmonary hypertension of the newborn were presented.Key words: smooth muscle biophysics, smooth muscle biochemistry, energetics of smooth muscle, pathophysiology of smooth muscle.

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Paving the way for transgenic schistosomes

Parasitology ◽

10.1017/s0031182011001466 ◽

2011 ◽

Vol 139 (5) ◽

pp. 651-668 ◽

Cited By ~ 21

Author(s):

S. BECKMANN ◽

C. G. GREVELDING

Keyword(s):

Rna Interference ◽

Initial Phase ◽

Functional Characterization ◽

Reporter Genes ◽

Significant Progress ◽

Gene Insertion ◽

Remarkable Progress ◽

Made In ◽

Silence Gene

SUMMARYIn parasitological research, significant progress has been made with respect to genomics and transcriptomics but transgenic systems for functional gene analyses are mainly restricted to the protozoan field. Gene insertion and knockout strategies can be applied to parasitic protozoa as well as gene silencing by RNA interference (RNAi). By contrast, research on parasitic helminthes still lags behind. Along with the major advances in genome and transcriptome analyses e.g. for schistosomes, methods for the functional characterization of genes of interest are still in their initial phase and have to be elaborated now, at the beginning of the post-genomic era. In this review we will summarize attempts made in the last decade regarding the establishment of protocols to transiently and stably transform or transfect schistosomes. Besides approaches using particle bombardment, electroporation or virus-based infection strateies to introduce DNA constructs into adult and larval schistosome stages to express reporter genes, first approaches have also been made in establishing protocols based on soaking, lipofection, and/or electroporation for RNA interference to silence gene activity. Although in these cases remarkable progress can be seen, the schistosome community eagerly awaits major breakthroughs especially with respect to stable transformation, but also for silencing or knock-down strategies for every schistosome gene of interest.

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