Devinder Arora

Bio: Devinder Arora is an academic researcher from Griffith University. The author has contributed to research in topics: Ventral tegmental area & Dopaminergic. The author has an hindex of 16, co-authored 44 publications receiving 1004 citations. Previous affiliations of Devinder Arora include University of Illinois at Chicago & Manipal University.

Cellular Effects of Pyocyanin, a Secreted Virulence Factor of Pseudomonas aeruginosa.

Abstract: Pyocyanin has recently emerged as an important virulence factor produced by Pseudomonas aeruginosa. The redox-active tricyclic zwitterion has been shown to have a number of potential effects on various organ systems in vitro, including the respiratory, cardiovascular, urological, and central nervous systems. It has been shown that a large number of the effects to these systems are via the formation of reactive oxygen species. The limitations of studies are, to date, focused on the localized effect of the release of pyocyanin (PCN). It has been postulated that, given its chemical properties, PCN is able to readily cross biological membranes, however studies have yet to be undertaken to evaluate this effect. This review highlights the possible manifestations of PCN exposure; however, most studies to date are in vitro. Further high quality in vivo studies are needed to fully assess the physiological manifestations of PCN exposure on the various body systems.

Molecular mechanisms underlying the effects of statins in the central nervous system

Abstract: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly referred to as statins, are widely used in the treatment of dyslipidaemia, in addition to providing primary and secondary prevention against cardiovascular disease and stroke. Statins' effects on the central nervous system (CNS), particularly on cognition and neurological disorders such as stroke and multiple sclerosis, have received increasing attention in recent years, both within the scientific community and in the media. Current understanding of statins' effects is limited by a lack of mechanism-based studies, as well as the assumption that all statins have the same pharmacological effect in the central nervous system. This review aims to provide an updated discussion on the molecular mechanisms contributing to statins' possible effects on cognitive function, neurodegenerative disease, and various neurological disorders such as stroke, epilepsy, depression and CNS cancers. Additionally, the pharmacokinetic differences between statins and how these may result in statin-specific neurological effects are also discussed.

Treatment with a novel hemigramicidin-TEMPO conjugate prolongs survival in a rat model of lethal hemorrhagic shock.

Abstract: Objective: We sought to develop a therapeutic agent that would permit prolongation of survival in rats subjected to lethal hemorrhagic shock (HS), even in the absence of resuscitation with asanguinous fluids or blood. Methods and Results: We synthesized a series of compounds that consist of the electron scavenger and superoxide dismutase mimic, 4-amino-2,2,6,6-tetramethylpiperidine-N-oxyl (4-NH2-TEMPO), conjugated to fragments and analogs of the membrane-active cyclopeptide antibiotic, gramicidin S. Using an in vivo assay, wherein isolated intestinal segments were loaded inside the lumen with various test compounds, we studied these compounds for their ability to prevent ileal mucosal barrier dysfunction induced by subjecting rats to profound HS for 2 hours. The most active compound in this assay, XJB-5-131, ameliorated peroxidation of the mitochondrial phospholipid, cardiolipin, in ileal mucosal samples from rats subjected to HS. XJB-5-131 also ameliorated HS-induced activation of the pro-apoptotic enzymes, caspases 3 and 7, in ileal mucosa. Intravenous treatment with XJB-5-131 (2 mol/kg) significantly prolonged the survival of rats subjected to profound blood loss (33.5 mL/kg) despite administration of only a minimal volume of crystalloid solution (2.8 mL/kg) and the absence of blood transfusion. Conclusion: These data support the view that mitochondrially targeted electron acceptors and SOD mimics are potentially valuable therapeutics for the treatment of serious acute conditions, such as HS, which are associated with marked tissue ischemia.

Protection against Radiotherapy-Induced Toxicity.

Abstract: Radiation therapy is a highly utilized therapy in the treatment of malignancies with up to 60% of cancer patients receiving radiation therapy as a part of their treatment regimen. Radiation therapy does, however, cause a wide range of adverse effects that can be severe and cause permanent damage to the patient. In an attempt to minimize these effects, a small number of compounds have been identified and are in use clinically for the prevention and treatment of radiation associated toxicities. Furthermore, there are a number of emerging therapies being developed for use as agents that protect against radiation-induced toxicities. The aim of this review was to evaluate and summarise the evidence that exists for both the known radioprotectant agents and the agents that show promise as future radioprotectant agents.

Epigenetic Regulations of GABAergic Neurotransmission: Relevance for Neurological Disorders and Epigenetic Therapy

Abstract: The GABAergic neurotransmission is a highly conserved system that has been attributed to various regulatory events. There has been a notable number of studies on the importance of GABAergic neurotrans

Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence.

Abstract: Pseudomonas aeruginosa is an opportunistic pathogen affecting immunocompromised patients. It is known as the leading cause of morbidity and mortality in cystic fibrosis (CF) patients and as one of the leading causes of nosocomial infections. Due to a range of mechanisms for adaptation, survival and resistance to multiple classes of antibiotics, infections by P. aeruginosa strains can be life-threatening and it is emerging worldwide as public health threat. This review highlights the diversity of mechanisms by which P. aeruginosa promotes its survival and persistence in various environments and particularly at different stages of pathogenesis. We will review the importance and complexity of regulatory networks and genotypic-phenotypic variations known as adaptive radiation by which P. aeruginosa adjusts physiological processes for adaptation and survival in response to environmental cues and stresses. Accordingly, we will review the central regulatory role of quorum sensing and signaling systems by nucleotide-based second messengers resulting in different lifestyles of P. aeruginosa. Furthermore, various regulatory proteins will be discussed which form a plethora of controlling systems acting at transcriptional level for timely expression of genes enabling rapid responses to external stimuli and unfavorable conditions. Antibiotic resistance is a natural trait for P. aeruginosa and multiple mechanisms underlying different forms of antibiotic resistance will be discussed here. The importance of each mechanism in conferring resistance to various antipseudomonal antibiotics and their prevalence in clinical strains will be described. The underlying principles for acquiring resistance leading pan-drug resistant strains will be summarized. A future outlook emphasizes the need for collaborative international multidisciplinary efforts to translate current knowledge into strategies to prevent and treat P. aeruginosa infections while reducing the rate of antibiotic resistance and avoiding the spreading of resistant strains.

Ventral tegmental area: cellular heterogeneity, connectivity and behaviour.

Abstract: Neurons in the ventral tegmental area (VTA) are highly heterogeneous and project to a range of different brain regions. Morales and Margolis summarize recent efforts to characterise VTA neurons, dissect their circuitry and understand their roles in motivation- and reward-related behaviours. Dopamine-releasing neurons of the ventral tegmental area (VTA) have central roles in reward-related and goal-directed behaviours. VTA dopamine-releasing neurons are heterogeneous in their afferent and efferent connectivity and, in some cases, release GABA or glutamate in addition to dopamine. Recent findings show that motivational signals arising from the VTA can also be carried by non-dopamine-releasing projection neurons, which have their own specific connectivity. Both dopamine-releasing and non-dopamine-releasing VTA neurons integrate afferent signals with local inhibitory or excitatory inputs to generate particular output firing patterns. Various individual inputs, outputs and local connections have been shown to be sufficient to generate reward- or aversion-related behaviour, indicative of the impressive contribution of this small population of neurons to behaviour.

Dopamine neurons modulate neural encoding and expression of depression-related behaviour

Abstract: Major depression is characterized by diverse debilitating symptoms that include hopelessness and anhedonia. Dopamine neurons involved in reward and motivation are among many neural populations that have been hypothesized to be relevant, and certain antidepressant treatments, including medications and brain stimulation therapies, can influence the complex dopamine system. Until now it has not been possible to test this hypothesis directly, even in animal models, as existing therapeutic interventions are unable to specifically target dopamine neurons. Here we investigated directly the causal contributions of defined dopamine neurons to multidimensional depression-like phenotypes induced by chronic mild stress, by integrating behavioural, pharmacological, optogenetic and electrophysiological methods in freely moving rodents. We found that bidirectional control (inhibition or excitation) of specified midbrain dopamine neurons immediately and bidirectionally modulates (induces or relieves) multiple independent depression symptoms caused by chronic stress. By probing the circuit implementation of these effects, we observed that optogenetic recruitment of these dopamine neurons potently alters the neural encoding of depression-related behaviours in the downstream nucleus accumbens of freely moving rodents, suggesting that processes affecting depression symptoms may involve alterations in the neural encoding of action in limbic circuitry.