Stress and addiction : contribution of the corticotropin releasing factor (CRF) system in neuroplasticity

Corticotropin releasing factor (CRF) has been shown to induce various behavioral changes related to adaptation to stress. Dysregulation of the CRF system at any point can lead to a variety of psychiatric disorders, including substance use disorders (SUDs). CRF has been associated with stress-induced drug reinforcement. Extensive literature has identified CRF to play an important role in the molecular mechanisms that lead to an increase in susceptibility that precipitates relapse to SUDs. The CRF system has a heterogeneous role in SUDs. It enhances the acute effects of drugs of abuse and is also responsible for the potentiation of drug-induced neuroplasticity evoked during the withdrawal period. We present in this review the brain regions and circuitries where CRF is expressed and may participate in stress-induced drug abuse. Finally, we attempt to evaluate the role of modulating the CRF system as a possible therapeutic strategy for treating the dysregulation of emotional behaviors that result from the acute positive reinforcement of substances of abuse as well as the negative reinforcement produced by withdrawal.

Neuronal nicotinic acetylcholine receptors : neuroplastic changes underlying alcohol and nicotine addictions

Addictive drugs can activate systems involved in normal reward-related learning, creating long-lasting memories of the drug's reinforcing effects and the environmental cues surrounding the experience. These memories significantly contribute to the maintenance of compulsive drug use as well as cue-induced relapse which can occur even after long periods of abstinence. Synaptic plasticity is thought to be a prominent molecular mechanism underlying drug-induced learning and memories. Ethanol and nicotine are both widely abused drugs that share a common molecular target in the brain, the neuronal nicotinic acetylcholine receptors (nAChRs). The nAChRs are ligand-gated ion channels that are vastly distributed throughout the brain and play a key role in synaptic neurotransmission. In this review, we will delineate the role of nAChRs in the development of ethanol and nicotine addiction. We will characterize both ethanol and nicotine's effects on nAChR-mediated synaptic transmission and plasticity in several key brain areas that are important for addiction. Finally, we will discuss some of the behavioral outcomes of drug-induced synaptic plasticity in animal models. An understanding of the molecular and cellular changes that occur following administration of ethanol and nicotine will lead to better therapeutic strategies.

Discovery and replication of gene influences on brain structure using LASSO regression

We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2.We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8±2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain.

No specific role for the manual motor system in processing the meanings of words related to the hand

The present study explored whether semantic and motor systems are functionally interwoven via the use of a dual-task paradigm. According to embodied language accounts that propose an automatic and necessary involvement of the motor system in conceptual processing, concurrent processing of hand-related information should interfere more with hand movements than processing of unrelated body-part (i.e., foot, mouth) information. Across three experiments, 100 right-handed participants performed left- or right-hand tapping movements while repeatedly reading action words related to different body-parts, or different body-part names, in both aloud and silent conditions. Concurrent reading of single words related to specific body-parts, or the same words embedded in sentences differing in syntactic and phonological complexity (to manipulate context-relevant processing), and reading while viewing videos of the actions and body-parts described by the target words (to elicit visuomotor associations) all interfered with right-hand but not left-hand tapping rate. However, this motor interference was not affected differentially by hand-related stimuli. Thus, the results provide no support for proposals that body-part specific resources in cortical motor systems are shared between overt manual movements and meaning-related processing of words related to the hand.

Metabolic efficiency with fast spiking in the squid axon

Fundamentally, action potentials in the squid axon are consequence of the entrance of sodium ions during the depolarization of the rising phase of the spike mediated by the outflow of potassium ions during the hyperpolarization of the falling phase. Perfect metabolic efficiency with a minimum charge needed for the change in voltage during the action potential would confine sodium entry to the rising phase and potassium efflux to the falling phase. However, because sodium channels remain open to a significant extent during the falling phase, a certain overlap of inward and outward currents is observed. In this work we investigate the impact of ion overlap on the number of the adenosine triphosphate (ATP) molecules and energy cost required per action potential as a function of the temperature in a Hodgkin–Huxley model. Based on a recent approach to computing the energy cost of neuronal action potential generation not based on ion counting, we show that increased firing frequencies induced by higher temperatures imply more efficient use of sodium entry, and then a decrease in the metabolic energy cost required to restore the concentration gradients after an action potential. Also, we determine values of sodium conductance at which the hydrolysis efficiency presents a clear minimum.

Neurotransmitter signaling in the pathophysiology of microglia

Erratun publicado en Frontiers in Cellular Neuroscience 7 : (2013) // Article ID 107

Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis

Microglia are the resident brain macrophages and they have been traditionally studied as orchestrators of the brain inflammatory response during infections and disease. In addition, microglia has a more benign, less explored role as the brain professional phagocytes. Phagocytosis is a term coined from the Greek to describe the receptor-mediated engulfment and degradation of dead cells and microbes. In addition, microglia phagocytoses brain-specific cargo, such as axonal and myelin debris in spinal cord injury or multiple sclerosis, amyloid-beta deposits in Alzheimer's disease, and supernumerary synapses in postnatal development. Common mechanisms of recognition, engulfment, and degradation of the different types of cargo are assumed, but very little is known about the shared and specific molecules involved in the phagocytosis of each target by microglia. More importantly, the functional consequences of microglial phagocytosis remain largely unexplored. Overall, phagocytosis is considered a beneficial phenomenon, since it eliminates dead cells and induces an anti-inflammatory response. However, phagocytosis can also activate the respiratory burst, which produces toxic reactive oxygen species (ROS). Phagocytosis has been traditionally studied in pathological conditions, leading to the assumption that microglia have to be activated inorder to become efficient phagocytes. Recent data, however, has shown that unchallenged microglia phagocytose apoptotic cells during development and in adult neurogenic niches, suggesting an overlooked role in brain remodeling throughout the normal lifespan. The present review will summarize the current state of the literature regarding the role of microglial phagocytosis in maintaining tissue homeostasis in health as in disease.

Infringement notices: stimulus for prevention or trivialising offences?

In the OHS field increasing use is being made of administrative penalties to enforce OHS legislation. Infringement notices (also known as penalty notices or on-the-spot fines) are used in several Australian jurisdictions and there are plans to introduce them in others. Overseas jurisdictions with some form of OHS administrative penalty include the United States, some Canadian provinces, and the system recently enacted in New Zealand. This article reviews empirical evidence and legal arguments about the use of infringement notices for enforcing OHS legislation. Key factors influencing the impact of these notices are discussed, including the monetary amounts of penalties, the nature of offences, the criteria and processes for issuing notices, and other implementation issues. There is a need for further empirical studies to determine the characteristics of infringement notice schemes that are most effective in motivating preventive action.

Submission to Communications Alliance Industry Code: Copyright Notice Scheme

In making this submission, we suggest that Australia learn from the experiences of other jurisdictions, and avoid some of the mistakes that have been made. In particular, this involves: * Ensuring that adequate information is available to evaluate the success of the scheme * Ensuring that notices sent to consumers provide full and accurate information that helps them understand their rights and options * Limiting the potential abuse of the system, and particularly attempts to intimidate consumers into paying unfair penalties through ‘speculative invoicing’ * Avoiding the potential for actual or perceived bias in the scheme’s oversight body

Essays on the history of Brazilian dipterology. I. The first notices about Brazilian Diptera (16th century)

Essays on the history of Brazilian dipterology. I. The first notices about Brazilian Diptera (16th century). This paper presents a historical resume of the first notices about Brazilian Diluent during the 16th century, given by Francisco Pires in 1552 (the oldest mention known), Jose de Anchieta, Leonardo do Valle, Pero de Magalhaes de Gandavo, Jean de Lery and Gabriel Soares de Souza, ending with Fernao Cardim, who made the last mentions of Brazilian Diptera in that century.

Essays on the history of Brazilian dipterology. II. Notices about Brazilian Diptera (17th century)

Essays on the history of Brazilian dipterology. II. Notices about Brazilian Diptera (17th century). Notices from the Brazilian Diptera from the 17th century come mainly from two foreign invasions occurred in Brazil, the first one by the French in Maranhao and the second by the Dutch in northeastern Brazil. This paper includes reports of Fathers Claude d'Abbeville and Yves d'Evreux and from Piso and Marcgrave, the last two presenting the first illustrations of Brazilian Diptera. The paper also includes reports of Friar Laureano de la Cruz, Father Joao de Sotto Mayor and Mauricio de Heriarte.

Essays on the history of Brazilian dipterology. III. Three remarkable notices from the 18th century, mainly related to myiasis-producing flies (Cochliomyia and Dermatobia)

Essays on the history of Brazilian dipterology. III. Three remarkable notices from the 18th century, mainly related to myiasis-producing flies (Cochliomyia and Dermatobia). This paper registers reports about dipterans made by three Portuguese who lived in Brazil during the 18th century. Luiz Gomes Ferreira, in his book "Erario mineral" ["Mineral revenue"], wrote curious passages related with myiasis-causing flies of the genus Cochliomyia. Jose Rodrigues de Mello registered, in Latin verses, the folklore for curing myiases caused by Cochliomyia hominivorax in cattle. Luiz dos Santos Vilhena, in the last of his twenty letters dealing with several aspects of life in Brazil, made reference to horseflies, human bot flies and mosquitos.

The law, practice, and procedure, relating to patents, designs, and trade marks : containing the Patents, Designs, and Trade Marks Act, 1882 : with the rules and forms, and the official instructions, regulations, and notices issued in pursuance of the act : and also the law officers' rules, and Privy Council rules : with full notes and comments /

Includes bibliographical references and index.