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EPHAR Lecture of the Month — November 2014

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Karl Deisseroth
D.H. Chen Professor of Bioengineering and of Psychiatry and Behavioral Sciences, Stanford University

"Circuit dynamics of adaptive and maladaptive behaviour"

The recent development of technologies for investigating specific components of intact biological systems has allowed elucidation of the neural circuitry underlying adaptive and maladaptive behaviours. Investigators are now able to observe and control, with high spatio-temporal resolution, structurally defined intact pathways along which electrical activity flows during and after the performance of complex behaviours. These investigations have revealed that control of projection-specific dynamics is well-suited to modulating behavioural patterns that are relevant to a broad range of psychiatric diseases. Structural dynamics principles have emerged to provide diverse, unexpected and causal insights into the operation of intact and diseased nervous systems, linking form and function in the brain.

(Keynote Lecture. Saturday 18 October 2014. 27th ECNP Congress. Berlin, Germany)

EPHAR Lecture of the Month — October 2014

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John A. Cidlowski
Signal Transduction Laboratory/Molecular Endocrinology Group, NIEHS, NIH, North Carolina (USA)

"The Heartbreak of Studying Corticosteroid Receptors at the NIH"

Glucocorticoids are the most commonly prescribed anti-inflammatory/immunosuppressant medications worldwide. This article highlights the risk of clinically significant and sometimes severe psychological, cognitive, and behavioral disturbances that may be associated with glucocorticoid use, as well as ways to prevent and treat these disturbances. ...

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(Lecture presented at XVII SIF (Italian Society of Pharmacology) national seminar for PhD students. Lectio Magistralis. 17th September 2014, Rimini, Italy)

EPHAR Lecture of the Month — September 2014

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Gian Marco Leggio
Department of Clinical and Molecular Biomedicine, University of Catania

"Dopamine D3 receptors and alcohol addiction"

Mesolimbic dopamine (DA) controls drug- and alcohol-seeking behavior, but the role of specific DA receptor subtypes is unclear. We tested the hypothesis that D3R gene deletion or the D3R pharmacological blockade inhibits ethanol preference in mice. D3R-deficient mice (D3R(−/−)) and their wild-type (WT) littermates, treated or not with the D3R antagonists SB277011A and U99194A, were tested in a long-term free choice ethanol-drinking (two-bottle choice) and in a binge-like ethanol-drinking paradigm (drinking in the dark, DID). ...

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(Lecture given at the 17th World Congress of Basic & Clinical Pharmacology (WCP 2014), during the EPHAR special lecture "The addictive brain through different receptor subtypes" (Cape Town, 15 July 2014))

EPHAR Lecture of the Month — July 2014

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Cristina Missale
Department of Molecular and Translational Medicine, University of Brescia

"The neurobiology of dopamine receptors: evolution from the dual concept to heterodimer complexes"

Dopamine (DA) controls different functions in the central nervous system, including locomotor activity, attention, motivation and positive reinforcement, by interacting with five different G protein-coupled receptors (GPCR). The first direct evidence for existence of two different DA receptors oppositely coupled to adenylyl cyclase (AC) was reported in 1978; the receptor associated to AC stimulation was referred to as D1 while that inhibiting cAMP system as D2. The dual receptor concept was the paradigm for DA receptor classification until gene cloning revealed a higher degree of complexity within DA receptors than previously thought. ...

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(Lecture given at the 12th Annual Summer School in Neuroscience of the International PhD program in Neuroscience, University of Catania, Italy; June 28 – July 4, Catania, Italy)

EPHAR Lecture of the Month — June 2014

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Naj Sharif
Pharmaceutical Regulatory Affairs at Alcon-Novartis, and adjunct professor at University of North Texas and Texas Southern University in Houston, TX, USA

"Pharmacological Evidence for Serotonin-2B Receptor-Mediated Bovine Ciliary Muscle Contraction"

The purpose of the research was to use receptor-selective agonists and antagonists to determine the pharmacological identity of receptors for serotonin (5-hydroxytryptamine, 5HT) involved in contracting bovine ciliary muscle (CM) in vitro. ...

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(Lecture given at the Physiology/Pharmacology section of the ARVO (Association for Research in Vision and Ophthalmology) Annual Meeting 4–8 May 2014, Orlando, FL, USA)

EPHAR Lecture of the Month — May 2014

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William Rostene
Emeritus Research Director at INSERM, working in the Vision Institute in Paris, France

"Chemokines: Neuropeptides that Umberto could not know during his research time"

Among the multiple works Prof. Umberto Scapagnini did during his fruitful scientific carrier, he was pioneer in the idea that the neuroendocrine systems can be linked to immunology (Bernardini R. et al.: Clin Pharmacol 1992). Chemokines are important messengers in immunological processes. They are small secreted proteins belonging to the cytokine family, originally defined as chemoattractants for leucocytes. Our group provided evidence that they are also expressed in the central nervous system where they are not only involved in inflammatory processes, ontogenesis, intercellular communication, but play a critical role in both basal and induced neuroendocrine effects. ...

read more... (Lecture given at the ECNP Workshop for Junior Scientists in Europe. 6–9 March 2014, Nice, France)

EPHAR Lecture of the Month — April 2014

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Eric Courchesne
UC San Diego Autism Center of Excellence (ACE Center), Department of Neuroscience, UC San Diego, San Diego, USA

"Autism is prenatal in origin: novel postmortem and in vivo studies of genomic, neural and functional defects"

Autism is a neural disorder impairing the early development of higher-order social, emotional and communication functions. Knowledge of the early underlying genomic, cellular, laminar and neurofunctional developmental pathologies in autism is prerequisite to creating valid animal models and more precise gene-brain and brain-behavior theories of autism. Such knowledge could lead to discovery of early diagnostic and prognostic biomarkers of risk for autism in babies and toddlers.

(Lecture given at the ECNP Workshop for Junior Scientists in Europe. 6–9 March 2014, Nice, France)

EPHAR Lecture of the Month — March 2014

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Paolo De Coppi
Reader and Consultant Paediatric Surgeon, Head of Surgery Unit at UCL Institute of Child Health and Great Ormond Street Hospital, London, UK

"Stem cells for the development of organs"

Regenerative medicine is a relatively new field, combining tissue engineering and cell transplantation, with the aim of replacing damaged tissues and organs using living cells. So far, most attention has focused on degenerative diseases such as cardiac failure, Parkinson's disease or Alzheimer's disease, while very little has been achieved in the treatment of congenital conditions. However, stem cell biology and regenerative medicine could lead to new ways of repairing or replacing injured organs, even during fetal development and therefore even children could benefit from this new exciting field.

(Lecture given at the NanoMED conference, 26–28 February 2014, University College London, Royal Free Hospital Campus, United Kingdom)

EPHAR Lecture of the Month — February 2014

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Barbara Kahn
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

"Novel Mechanisms by Which Adipose Tissue Alters Systemic Insulin Sensitivity and Diabetes Risk"

Resistance to insulin-stimulated glucose transport and metabolism is a major pathogenic factor in type 2 diabetes and contributes to the morbidity of obesity. Down-regulation of human and mouse adipose tissue glucose transporter occurs early in diabetes development. Mice, with "knockout" or overexpression of the GLUT4 glucose transporter selectively in adipose tissue, have been made. Characterization of these mice led to novel insights including the important role of adipocytes in regulating glucose homeostasis and insulin sensitivity through the secretion of hormones, cytokines and other factors. Moreover, novel molecules expressed in adipoctyes and involved in adipocyte function and systemic insulin sensitivity, have been identified and validated.

read more... (Lecture presented at the Salk Institute, Fondation Ipsen, Nature Symposium; La Jolla, CA (29-31 January 2014). Section-Control of Energy Balance)

EPHAR Lecture of the Month — January 2014

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Gerhardt Attard
The Institute of Cancer Research and the Royal Marsden, UK

"Abiraterone; a selective, oral CYP17 inhibitor for the treatment of metastatic, castration resistant prostate cancer"

A significant proportion of castration-resistant prostate cancers (CRPC) remains driven by ligand activation of the androgen receptor. Although the testes are the primary source of testosterone, testosterone can also be produced from peripheral conversion of adrenal sex hormone precursors DHEA and androstenedione in the prostate and other tissues. CYP17A1 catalyzes two essential reactions in the production of DHEA and androstenedione: the hydroxylation (hydroxylase activity) and the subsequent cleavage of the C17–20 side chain (lyase activity). Potent and selective inhibition of CYP17A1 by abiraterone depletes residual nongonadal androgens and is an effective treatment for CRPC. Elucidation of the mechanisms that underlie resistance to abiraterone will inform the development of novel therapeutic strategies post-abiraterone. Preclinical evidence that androgen biosynthesis in prostate cancer cells does not necessarily follow a single dominant pathway, and residual androgens or alternative ligands (including administered glucocorticoids) can reactivate androgen receptor signaling, supports cotargeting of more than one enzyme involved in steroidogenesis and combining a CYP17A1 inhibitor with an antiandrogen. Furthermore, given the drawbacks of 17α-hydroxylase inhibition, there is considerable interest in developing new CYP17A1 inhibitors that more specifically inhibit lyase activity and are therefore less likely to require glucocorticoid coadministration.

(Lecture presented at Pharmacology 2013, London, UK, section "Drug discovery of the year: the key role of pharmacology" on 19 December 2013)

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EPHAR Lecture of the Month — December 2013

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Bryan L. Roth
Department of Pharmacology, University of North Carolina at Chapel Hill, USA

"DREADDs: novel tools for drug discovery and development"

"DREADD" (Designer Receptor Exclusively Activated by Designer Drug) is a new synthetic biology technology which allows for the remote control of cellular signaling. DREADD can be used to identify neuronal and non-neuronal networks essential for psychoactive drug actions. Since the invention of the first DREADDs, these engineered G protein-coupled receptors (GPCRs) have been widely applied in investigations of biological processes and behaviors. DREADD technology has emerged as a powerful tool with great potential for drug discovery and development. DREADDs can facilitate the identification of druggable targets and enable researchers to explore the activities of novel drugs against both known and orphan GPCRs. DREADDs can be used as novel tools for drug discovery and development.

(Lecture presented at Neuroscience, 9–13 November 2013 (Theme: Novel Methods and Technology Development), San Diego USA)

EPHAR Lecture of the Month — November 2013

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Roberto Ciccocioppo
School of Pharmacy, Pharmacology Unit, University of Camerino

"Translational approach to develop novel medications on alcohol addiction: focus on neuropeptides"

Research on alcohol and drug dependence has shown that the development of addiction depends on a complex interplay of psychological factors, genetic or epigenetic predisposing factors, and neurobiological adaptations induced by drug consumption. A greater understanding of the mechanisms leading to alcohol abuse will allow researchers to identify genetic variation that corresponds to a specific biological vulnerability to addiction, thus defining robust endophenotypes that might help deconstruct these complex syndromes into more tractable components. To this end, it is critical to develop a translational framework that links alterations at the molecular level, to changes in neuronal function, and ultimately to changes at the behavioral and clinical levels. Translational phenotypes can be identified by the combination of animal and human studies designed to elucidate the neurofunctional, anatomical and pharmacological mechanisms underlying the etiology of alcohol addiction. The present article offers an overview of medication development in alcoholism with a focus on the critical aspect of translational research. Moreover, significant examples of promising targets from neuropeptidergic systems, namely nociceptin/orphanin FQ and neuropeptide S are given.

(Lecture at the SIF-EPHAR Symposium held in Turin, October 25, 2013)

 

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