scholarly journals Genetic variation in alcoholism and opioid addiction susceptibility and treatment: a pharmacogenomic approach

2021 ◽  
Vol 8 (4) ◽  
pp. 202-222
Author(s):  
Catherine Demery-Poulos ◽  
◽  
Joseph M. Chambers
Keyword(s):  
Genetic Predisposition ◽  
Current Knowledge ◽  
Opioid Addiction ◽  
Opioid Abuse ◽  
Epistatic Interactions ◽  
Societal Level ◽  
Reward Pathway ◽  
The Individual ◽  
New Research ◽  
The Brain

<abstract> <p>Alcohol and opioid abuse have pervasive and detrimental consequences from the individual to societal level. The extent of genetic contribution to alcoholism has been studied for decades, yielding speculative and often inconsistent results since the previous discovery of two pharmacokinetic variants strongly protective against alcoholism. The neurobiology of addiction involves innumerate genes with combinatorial and epistatic interactions, creating a difficult landscape for concrete conclusions. In contrast, pharmacogenomic variation in the treatment of alcoholism yields more immediate clinical utility, while also emphasizing pathways crucial to the progression of addiction. An improved understanding of genetic predisposition to alcohol abuse has inherent significance for opioid addiction and treatment, as the two drugs induce the same reward pathway. This review outlines current knowledge, treatments, and research regarding genetic predisposition to alcoholism, focusing on pharmacodynamic variation within the dopaminergic system and shared implications for opioid abuse. Multifaceted and highly polygenic, the phenotype of addiction seems to grow more complex as new research extends the scope of its impact on the brain, body, and progeny.</p> </abstract>

scholarly journals Astroglial Isopotentiality and Calcium-Associated Biomagnetic Field Effects on Cortical Neuronal Coupling

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 439
Author(s):  
Marcos Martinez-Banaclocha
Keyword(s):  
Current Knowledge ◽  
Critical Role ◽  
Brain Regions ◽  
Local Magnetic Field ◽  
Field Potentials ◽  
Coherent Integration ◽  
Cognitive Faculties ◽  
Synaptic Neurotransmission ◽  
New Research ◽  
The Brain

Synaptic neurotransmission is necessary but does not sufficiently explain superior cognitive faculties. Growing evidence has shown that neuron–astroglial chemical crosstalk plays a critical role in the processing of information, computation, and memory. In addition to chemical and electrical communication among neurons and between neurons and astrocytes, other nonsynaptic mechanisms called ephaptic interactions can contribute to the neuronal synchronization from different brain regions involved in the processing of information. New research on brain astrocytes has clearly shown that the membrane potential of these cells remains very stable among neighboring and distant astrocytes due to the marked bioelectric coupling between them through gap junctions. This finding raises the possibility that the neocortical astroglial network exerts a guiding template modulating the excitability and synchronization of trillions of neurons by astroglial Ca2+-associated bioelectromagnetic interactions. We propose that bioelectric and biomagnetic fields of the astroglial network equalize extracellular local field potentials (LFPs) and associated local magnetic field potentials (LMFPs) in the cortical layers of the brain areas involved in the processing of information, contributing to the adequate and coherent integration of external and internal signals. This article reviews the current knowledge of ephaptic interactions in the cerebral cortex and proposes that the isopotentiality of cortical astrocytes is a prerequisite for the maintenance of the bioelectromagnetic crosstalk between neurons and astrocytes in the neocortex.

scholarly journals The mysteries of remote memory

2018 ◽  
Vol 373 (1742) ◽  
pp. 20170029 ◽  
Author(s):  
Zimbul Albo ◽  
Johannes Gräff
Keyword(s):  
Memory Consolidation ◽  
Current Knowledge ◽  
Standard Theory ◽  
Remote Memory ◽  
Cortical Networks ◽  
Exciting Field ◽  
The Individual ◽  
Time Information ◽  
The Brain ◽  
Multiple Trace Theory

Long-lasting memories form the basis of our identity as individuals and lie central in shaping future behaviours that guide survival. Surprisingly, however, our current knowledge of how such memories are stored in the brain and retrieved, as well as the dynamics of the circuits involved, remains scarce despite seminal technical and experimental breakthroughs in recent years. Traditionally, it has been proposed that, over time, information initially learnt in the hippocampus is stored in distributed cortical networks. This process—the standard theory of memory consolidation—would stabilize the newly encoded information into a lasting memory, become independent of the hippocampus, and remain essentially unmodifiable throughout the lifetime of the individual. In recent years, several pieces of evidence have started to challenge this view and indicate that long-lasting memories might already ab ovo be encoded, and subsequently stored in distributed cortical networks, akin to the multiple trace theory of memory consolidation. In this review, we summarize these recent findings and attempt to identify the biologically plausible mechanisms based on which a contextual memory becomes remote by integrating different levels of analysis: from neural circuits to cell ensembles across synaptic remodelling and epigenetic modifications. From these studies, remote memory formation and maintenance appear to occur through a multi-trace, dynamic and integrative cellular process ranging from the synapse to the nucleus, and represent an exciting field of research primed to change quickly as new experimental evidence emerges. This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.

scholarly journals The Diversity of Intermediate Filaments in Astrocytes

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1604 ◽  
Author(s):  
Maja Potokar ◽  
Mitsuhiro Morita ◽  
Gerhard Wiche ◽  
Jernej Jorgačevski
Keyword(s):  
Intermediate Filaments ◽  
Current Knowledge ◽  
Cell Types ◽  
Multiple Roles ◽  
Cellular Structures ◽  
Cellular Processes ◽  
Different Types ◽  
The Individual ◽  
Neuronal Functions ◽  
The Brain

Despite the remarkable complexity of the individual neuron and of neuronal circuits, it has been clear for quite a while that, in order to understand the functioning of the brain, the contribution of other cell types in the brain have to be accounted for. Among glial cells, astrocytes have multiple roles in orchestrating neuronal functions. Their communication with neurons by exchanging signaling molecules and removing molecules from extracellular space takes place at several levels and is governed by different cellular processes, supported by multiple cellular structures, including the cytoskeleton. Intermediate filaments in astrocytes are emerging as important integrators of cellular processes. Astrocytes express five types of intermediate filaments: glial fibrillary acidic protein (GFAP); vimentin; nestin; synemin; lamins. Variability, interactions with different cellular structures and the particular roles of individual intermediate filaments in astrocytes have been studied extensively in the case of GFAP and vimentin, but far less attention has been given to nestin, synemin and lamins. Similarly, the interplay between different types of cytoskeleton and the interaction between the cytoskeleton and membranous structures, which is mediated by cytolinker proteins, are understudied in astrocytes. The present review summarizes the basic properties of astrocytic intermediate filaments and of other cytoskeletal macromolecules, such as cytolinker proteins, and describes the current knowledge of their roles in normal physiological and pathological conditions.

Fit Vs Faint: Assessing Work Causation in “Idiopathic Fall” Cases

2014 ◽  
Vol 19 (5) ◽  
pp. 3-12
Author(s):  
Lorne Direnfeld ◽  
David B. Torrey ◽  
Jim Black ◽  
LuAnn Haley ◽  
Christopher R. Brigham
Keyword(s):  
Blood Flow ◽  
Electrical Activity ◽  
Loss Of Consciousness ◽  
Brain Electrical Activity ◽  
Medical Terminology ◽  
Scientific Analysis ◽  
Medical Causation ◽  
The Individual ◽  
The Brain ◽  
Current Science

Abstract When an individual falls due to a nonwork-related episode of dizziness, hits their head and sustains injury, do workers’ compensation laws consider such injuries to be compensable? Bearing in mind that each state makes its own laws, the answer depends on what caused the loss of consciousness, and the second asks specifically what happened in the fall that caused the injury? The first question speaks to medical causation, which applies scientific analysis to determine the cause of the problem. The second question addresses legal causation: Under what factual circumstances are injuries of this type potentially covered under the law? Much nuance attends this analysis. The authors discuss idiopathic falls, which in this context means “unique to the individual” as opposed to “of unknown cause,” which is the familiar medical terminology. The article presents three detailed case studies that describe falls that had their genesis in episodes of loss of consciousness, followed by analyses by lawyer or judge authors who address the issue of compensability, including three scenarios from Arizona, California, and Pennsylvania. A medical (scientific) analysis must be thorough and must determine the facts regarding the fall and what occurred: Was the fall due to a fit (eg, a seizure with loss of consciousness attributable to anormal brain electrical activity) or a faint (eg, loss of consciousness attributable to a decrease in blood flow to the brain? The evaluator should be able to fully explain the basis for the conclusions, including references to current science.

The Cooking Ape: An Interview with Richard Wrangham

2005 ◽  
Vol 5 (1) ◽  
pp. 29-37
Author(s):  
elisabeth townsend
Keyword(s):  
Social Relationships ◽  
Human Behavior ◽  
Homo Sapiens ◽  
Social Groups ◽  
Harvard University ◽  
Primate Research ◽  
Social Organizations ◽  
Cooked Food ◽  
New Research ◽  
The Brain

Humans: The Cooking Ape Perhaps the first to suggest that humans were cooking as early as 1.9 million years ago, Richard Wrangham shows through his new research and his imagination how and possibly when cooking changed humans dramatically. Wrangham, Harvard University primatologist and MacArthur Fellow, has been studying the evolution of human cooking. After 25 years of primate research at his site in Kibale, Uganda, Wrangham is best known for explaining the similarity and differences across species of primate social organizations. In Kibale, he has analyzed chimpanzees’ behavior: how it’s changed when they interact with the environment and how their social groups have evolved. In particular, he noticed how food changed their interactions with each other. Like that of chimps, human behavior has been affected by food, especially as they shifted from raw to cooked food. Moving from eating food as it was discovered to collecting edibles and cooking them altered our social relationships. Cooked food has changed Homo sapiens physically by making food more digestible thereby altering jaws, teeth, and guts, and providing more calories for more expensive organs such as the brain. Wrangham discusses when and how humans may have started using fire to cook food, what they cooked, and the transition from cooking in an outdoor fire to hearths and open ovens.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

Experimental Rodent Models of Vascular Dementia: A Systematic Review

2021 ◽  
Vol 19 ◽  
Author(s):  
Nidhi Tiwari ◽  
Jyoti Upadhyay ◽  
Mohd Nazam Ansari ◽  
Syed Shadab Raza ◽  
Wasim Ahmad ◽  
...  
Keyword(s):  
Vascular Dementia ◽  
Small Vessel Disease ◽  
Current Knowledge ◽  
Vascular Cognitive Impairment ◽  
Experimental Models ◽  
New Drugs ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
The Brain ◽  
Large Vessel Disease

: Vascular dementia (VaD) occurs due to cerebrovascular insufficiency, which leads to decreased blood circulation to the brain, thereby resulting in mental disabilities. The main causes of vascular cognitive impairment (VCI) are severe hypoperfusion, stroke, hypertension, large vessel disease (cortical), small vessel disease (subcortical VaD), strategic infarct, hemorrhage (microbleed), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and cerebral amyloid angiopathy (CAA),which leads to decreased cerebrovascular perfusion. Many metabolic disorders such as diabetes mellitus (DM), dyslipidemia, and hyperhomocysteinemia are also related to VaD. The rodent experimental models provide a better prospective for the investigation of the molecular mechanism of new drugs. A plethora of experimental models are available that mimic the pathological conditions and lead to VaD. This review article updates the current knowledge on the basis of VaD, risk factors, pathophysiology, mechanism, advantages, limitations, and the modification of various available rodent experimental models.

Where the Millennials Will Take Us

2018 ◽  
Author(s):  
Barbara J. Risman
Keyword(s):  
Young People ◽  
Life Stage ◽  
Structure Theory ◽  
Theoretical Argument ◽  
Individual Level ◽  
Gender Categories ◽  
The Individual ◽  
New Research ◽  
Fourth Wave

In this book Barbara J. Risman uses her gender structure theory to tackle the question about whether today’s young people, Millennials, are pushing forward the gender revolution or backing away from it. In the first part of the book, Risman revises her theoretical argument to differentiate more clearly between culture and material aspects of each level of gender as a social structure. She then uses previous research to explain that today’s young people spend years in a new life stage where they are emerging as adults. The new research presented here offers a typology of how today’s young people wrestle with gender during the years of emerging adulthood. How do they experience gender at the individual level? What are the expectations they face because of their sex? What are their ideological beliefs and organizational constraints based on their gender category? Risman suggests there is great variety within this generation. She identifies four strategies used by young people: true believers in gender difference, innovators who want to push boundaries in feminist directions, straddlers who are simply confused, and rebels who sometimes identify as genderqueer and reject gender categories all together. The final chapter offers a utopian vision that would ease the struggles of all these groups, a fourth wave of feminism that rejects the gender structure itself. Risman envisions a world where the sex ascribed at birth matters has few consequences beyond reproduction.

scholarly journals L2HGDH Missense Variant in a Cat with L-2-Hydroxyglutaric Aciduria

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 682
Author(s):  
Matthias Christen ◽  
Nils Janzen ◽  
Anne Fraser ◽  
Adrian C. Sewell ◽  
Vidhya Jagannathan ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Genetic Defect ◽  
Clinical Signs ◽  
Missense Variant ◽  
Microcytic Anemia ◽  
Abnormal Behavior ◽  
Functional Candidate Gene ◽  
History Of ◽  
The Brain ◽  
Hydroxyglutaric Acid

A 7-month-old, spayed female, domestic longhair cat with L-2-hydroxyglutaric aciduria (L-2-HGA) was investigated. The aim of this study was to investigate the clinical signs, metabolic changes and underlying genetic defect. The owner of the cat reported a 4-month history of multiple paroxysmal seizure-like episodes, characterized by running around the house, often in circles, with abnormal behavior, bumping into obstacles, salivating and often urinating. The episodes were followed by a period of disorientation and inappetence. Neurological examination revealed an absent bilateral menace response. Routine blood work revealed mild microcytic anemia but biochemistry, ammonia, lactate and pre- and post-prandial bile acids were unremarkable. MRI of the brain identified multifocal, bilaterally symmetrical and T2-weighted hyperintensities within the prosencephalon, mesencephalon and metencephalon, primarily affecting the grey matter. Urinary organic acids identified highly increased levels of L-2-hydroxyglutaric acid. The cat was treated with the anticonvulsants levetiracetam and phenobarbitone and has been seizure-free for 16 months. We sequenced the genome of the affected cat and compared the data to 48 control genomes. L2HGDH, coding for L-2-hydroxyglutarate dehydrogenase, was investigated as the top functional candidate gene. This search revealed a single private protein-changing variant in the affected cat. The identified homozygous variant, XM_023255678.1:c.1301A>G, is predicted to result in an amino acid change in the L2HGDH protein, XP_023111446.1:p.His434Arg. The available clinical and biochemical data together with current knowledge about L2HGDH variants and their functional impact in humans and dogs allow us to classify the p.His434Arg variant as a causative variant for the observed neurological signs in this cat.

scholarly journals The L1-dependant and Pol III transcribed Alu retrotransposon, from its discovery to innate immunity

2021 ◽  
Vol 48 (3) ◽  
pp. 2775-2789
Author(s):  
Ludwig Stenz
Keyword(s):  
Human Genome ◽  
Viral Infections ◽  
De Novo ◽  
Current Knowledge ◽  
Innate Immune ◽  
De Novo Mutation ◽  
Neuronal Diversity ◽  
Alu Sequences ◽  
Pol Iii ◽  
The Brain

AbstractThe 300 bp dimeric repeats digestible by AluI were discovered in 1979. Since then, Alu were involved in the most fundamental epigenetic mechanisms, namely reprogramming, pluripotency, imprinting and mosaicism. These Alu encode a family of retrotransposons transcribed by the RNA Pol III machinery, notably when the cytosines that constitute their sequences are de-methylated. Then, Alu hijack the functions of ORF2 encoded by another transposons named L1 during reverse transcription and integration into new sites. That mechanism functions as a complex genetic parasite able to copy-paste Alu sequences. Doing that, Alu have modified even the size of the human genome, as well as of other primate genomes, during 65 million years of co-evolution. Actually, one germline retro-transposition still occurs each 20 births. Thus, Alu continue to modify our human genome nowadays and were implicated in de novo mutation causing diseases including deletions, duplications and rearrangements. Most recently, retrotransposons were found to trigger neuronal diversity by inducing mosaicism in the brain. Finally, boosted during viral infections, Alu clearly interact with the innate immune system. The purpose of that review is to give a condensed overview of all these major findings that concern the fascinating physiology of Alu from their discovery up to the current knowledge.

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