Interview with the Coordinator Prof. Giuseppe Di Giovanni, University of Malta, Department of Physiology and Biochemistry

Interview with the Coordinator of the Malta Neuroscience Network Programme, Prof. Giuseppe Di Giovanni regarding the Malta Neuroscience Net- work. "With the creation of the Malta Neuroscience Network, we will be keeping up with the most important developments with regard to brain research world- wide: multi-disciplinary collaboration. Understanding the way the brain works, and above all brain diseases is extremely complicated, and requires the involvement of researchers coming from a number of diff erent scientifi c disciplines and clinical areas collaborating in new ways."peer-reviewe

Second Neuroscience Day at the University of Malta

The second Neuroscience Seminar Day @ the University of Malta was held on the 5th and 6th of July 2011 at the Faculty of Medicine and Surgery. The principal aim of this day was to create a forum in which Maltese and Italian neuroscientists could meet. Academics involved in this field benefit substantially by meeting and interacting with international colleagues, and thereby developing new collaborations. This view is held not only by myself, but also by Professor Richard Muscat, ProRector for Research and Innovation, who is always highly supportive of the development of the field of neuroscience and of research in general in Malta. My second objective in organising these neuroscience seminars is to offer the opportunity for our medical and science students and also the general public to get to know about new developments in the field of brain research achieved by both Maltese and foreign scientists.peer-reviewe

Nicotine addiction : a review

Nicotine, the major psychoactive compound in tobacco, acts as a potent addictive drug in humans. The addictive nature of nicotine leads to more than 6 million deaths a year. Evidence indicates that nicotine and other drugs of abuse act on central dopaminergic pathways and modulate their neurophysiological mechanisms. Nicotine stimulates dopaminergic pathways and the prefrontal cortex (PFC), inducing enhanced reward perception and increased cognitive function, respectively. These findings are consistent with the fact that nicotine binds to different subtypes of nicotinic acetylcholine receptors present on the neurons found in the PFC and ventral tegmental area of the midbrain. The latter, being the area most involved in addictive behaviour, projects on the limbic system, particularly the nucleus accumbens, and receives afferents from the prefrontal cortex and brainstem. Although dopaminergic pathways and nicotinic acetylcholine receptors are the protagonists of nicotine addiction, several minor pathways and their constituent receptors have been indicated as being either directly or indirectly affected by nicotine. These include serotonergic pathways and central cannabinoid receptors. Despite the scarcity of approved drugs and partial efficacy of approved treatment, insight into nicotine neurophysiological modulation led to better appreciation of nicotine-seeking behaviour and subsequent improved design of pharmacological and behavioural approaches to smoking cessation. Tobacco is the single most preventable cause of death in the world today. Better understanding of the neurobiological mechanisms underlying nicotine addiction will ultimately lead to more effective treatments of both nicotine dependence and nicotine rewarding effects.peer-reviewe

Interview with the Co-ordinator of the Malta Neuroscience Network

Iggy Fenech interviews the Co-ordinator of the Malta Neuroscience Network, Professor Giuseppe Di Giovanni. He is a neuroscientist. For more than 2 decades, his research has focused on understanding the patho- physiology of central monoaminergic systems in di fferent neuropsychiatric disorders such as depression, schizophrenia, drug abuse, Parkinson's disease and epilepsy.peer-reviewe

Is social identity belief independent?

In this paper we aim to disentangle the effects on in-group favoritism driven by beliefs from those stemming from group identity, with the final goal of testing the relative power of three potential explanations of this bias: The Beliefs Driven Explanation (BDE), the Group Identity Explanation (GIE) and the Belief-mediated Group Identity Explanation (BGE). The BDE suggests that in-group favoritism is only driven by the desire not to let others’ expectations down. The GIE claims that people have a preference, per se, for members of their group. According to the BGE, people also have a preference for members of their group, but this is mediated by their second-order beliefs. To this aim, we built an experimental design able to produce exogenous variations in both group membership and expectations, hence providing a genuine test for the rationale of in-group bias. The results of our experiment suggest that beliefs per se are not a significant explanation of in-group favoritism and hence do not provide support to the BDE. Our experimental evidence does not provide support also to the BGE. We conclude that our experiment suggests to single out the GIE as the most powerful explanation of social identity

Cannabis medicine offers hope for severe paediatric epilepsies

Science does not need to take a position on legalizing the recreational use of cannabis, this is more a political issue or a personal choice. Cannabis, as the other drugs of abuse, produces several detrimental effects on brain function but differently from alcohol, nicotine, cocaine, heroin and ecstasy (just to cite the most commune ab- used ones) these are mostly present with acute intoxication and disappear after termination of drug intake. Consequently, there is no scientific reason for which we have some legal drugs of abuse such as alcohol and tobacco sold by governments and others labelled as il- legal and banned by society. This is, of course, a flawed situation but one that illustrates a major paradox in international laws on drugs. Despite being illegal, cannabis is (ab)used by about 87.6 million European adults (23.7% of adults) (EMCDDA, 2017). Cannabis is also the most commonly used illicit drug among the Maltese adult population aged 18–65 years. According to the 2013 general population study, around 4.3% of those aged 18–65 years reported having used cannabis during their lifetime (EMCDDA, 2017).peer-reviewe

Does Central Serotonin2C Receptor still have New Therapeutic Potential?

Since the 1950s, when serotonin (5-HT) was discovered in the mammalian central nervous system (CNS), an enormous amount of experimental evidence has revealed the pivotal role of this biogenic amine in a number of cognitive and behavioural functions [1]. Although 5-HT is synthesized by a small group of neurons within the raphe nuclei of the brain stem, almost all parts of the CNS receive serotonergic projections. Furthermore, the importance of 5-HT modulation and the fine-tuning of its action are underlined by the large number of 5-HT binding sites found in the CNS. Hitherto, up to 15 different 5-HT receptors subtypes have been identified. Large amounts of experimental evidence have explored the pathophysiological role of one of these receptors, the 5-HT2C receptor, that has emerged as a prominent central serotonin receptor subtype. Since its discovery its discovery about 25 years ago by Palacios, Pazos and Hoyer, who named it 5-HT1C (see the book 5-HT2C Receptors in the Pathophysiology of CNS disease, 2011); it has been shown to play a major role in the regulation of a plethora of behaviours. Therefore, it is not surprising that experimental and clinical observations have highlighted it as a possible therapeutic target for the development of drugs for a range of CNS disorders such as schizophrenia, depression, drug abuse, eating disorders, Parkinson’s disease and epilepsy, to cite but a few. Thus, the 5-HT2C antagonism appears to be an important feature of antipsychotic and antidepressants drugs with broad pharmacological profiles, properties that probably contribute to the treatment of negative and depressive symptoms respectively, or to the mitigation of side-effects. Although several selective agents for this receptor have been discovered, none have reached the market for the treatment of CNS disorders to date, essentially as a result of their limited efficacy and related side effects. Indeed, most of the 5-HT2C ligands have binding affinity for the 5-HT2B receptors, which may limit its therapeutic potential given that action at peripheral 5-HT2B receptors is thought to underlie the cardiopulmonary complications associated with some serotonergic drugs. Several pharmaceutical companies are still very active in 5-HT2C receptors research. Nevertheless, the only compound with 5-HT2C affinity that has reached the market is agomelatine, released by Servier for the treatment of major depressive disorder with a reduced level of sexual side effects compared to some other antidepressants. Agomelatine is a melatonergic agonist (MT1 and MT2 receptors) and 5-HT2C antagonist. Probably, the next 5-HT2C compound to obtain the Food and Drug Administration (FDA) approval in the United States will be lorcaserin by Arena Pharmaceuticals, for the treatment of obesity. Lorcaserin shows 100 times higher affinity for 5-HT2C versus other receptors, the only drawback is the exposure-response relationship for lorcaserin-emergent mammary adenocarcinoma. However, given the results of the Pathology Working Group, this may no longer be of concern since there is no statistically significant increase in mammary risk for lorcaserin patients. Therefore, there is good chance for lorcaserin to gain the FDA approval later on during this year.peer-reviewe

Line-Recovery by Programmable Particles

Shape formation has been recently studied in distributed systems of programmable particles. In this paper we consider the shape recovery problem of restoring the shape when $f$ of the $n$ particles have crashed. We focus on the basic line shape, used as a tool for the construction of more complex configurations. We present a solution to the line recovery problem by the non-faulty anonymous particles; the solution works regardless of the initial distribution and number $f<n-4$ of faults, of the local orientations of the non-faulty entities, and of the number of non-faulty entities activated in each round (i.e., semi-synchronous adversarial scheduler)

Pathophysiological role of extrasynaptic GABAA receptors in typical absence epilepsy

GABA is the principal inhibitory neurotransmitter in the mammalian CNS. It acts via two classes of receptors, the GABAA, a ligand gated ion channel (ionotropic receptor) and the metabotropic G-protein coupled GABAB receptor. While synaptic GABAA receptors underlie classical ‘phasic’ GABAA receptor-mediated inhibition, extrasynaptic GABAA receptors (eGABAAR) mediate a new form of inhibition, termed ‘tonic’ GABAA inhibition. The subunit composition of eGABAARs differs from those present at the synapse, resulting in pharmacologically and functionally distinct properties. In this mini-review the findings presented at the 2nd Neuroscience Day meeting held last July in Malta will be summarised. Particular emphasis will be given to the important pathophysiological role of eGABAAR within thalamocortical circuits as a major player in nonconvulsive absence epilepsy. The new findings presented at the conference suggest that enhanced tonic inhibition is a common cause of seizures in several animal models of absence epilepsy and may provide new targets for therapeutic intervention.peer-reviewe