Scientific Program

Conference Series Ltd invites all the participants across the globe to attend International Conference on Brain Disorders and Therapeutics London, UK.

Day 3 :

  • Associated Disorders
Location: Guggenheim Room
Speaker

Chair

Kerensa Broersen

University of Twente, The Netherlands

Speaker

Co-Chair

Mehrdad Shamloo

Stanford University, USA

Session Introduction

Kerensa Broersen

University of Twente, The Netherlands

Title: The role of amyloid beta peptide variability toward progress of Alzheimer disease

Time : 09:30-09:50

Speaker
Biography:

In 1993 Kerensa started her study nutrition and dietetics in Amsterdam. After finishing the bachelor in 1997, she continued with a master degree nutrition and food management at Huddersfield University in the UK. From 2000 until 2005 she worked as a PhD student at Wageningen University on the biophysics of unfolding, refolding and aggregation of food related proteins. Her first postdoctoral work was at the Medical Research Council – Laboratory of Molecular Biology in the Neurobiology department in Cambridge, UK. This work focused on fatty acid – a-synuclein interactions employing both biophysics and cell culture as research tools. Her second postdoc was at the Free University of Brussels (VUB) in Belgium where she started working on the role of amyloid beta peptide in Alzheimer’s disease. Here she also obtained an Odysseus grant from the Belgian government and, as a result of that, was offered a position as assistant professor. Kerensa moved to her current position as an assistant professor at the University of Twente in March 2011. She prefers to spend her spare time in the dojo doing karate, travelling, gardening or reading.

Abstract:

Soluble aggregated forms of the beta amyloid peptide (Aβ) have been shown to play an important role in the progress of Alzheimer disease. This extracellular residing peptide arises from cleavage of transmembrane amyloid precursor protein through cleavage by means of a combination of secretase enzymes. As a result of this enzymatic processing, genetic profile and further modifications, the amyloid beta peptide does not exist as a well-defined species but arises in a variety of truncated and modified forms. For example, it has been reported that, within any one individual, a range of amyloid beta peptides exist varying in length from 34 to 49 amino acids and that multiple otherwise modified forms of this peptide are present in a complex mixture. By simple mixing of various ratios of Aβ1-40 and Aβ1-42, the two most prominent forms of the peptide present in the brain, we have already shown that small shifts in the ratio between these two peptides can have significant impact on the aggregation reaction, cellular response and cognitive behavior in animal models (1,2). These shifts are of biological relevance as it has also been reported that the presence of longer and more aggregation-prone Aβ1-42 slightly rises in patients with Alzheimer disease, sometimes at the cost of Aβ1-40 production. We extended our observations by also including Aβ1-38 and Aβ1-43 into the equation and found that inclusion of these peptides can alter the toxic profile of these peptides (3). Further investigations into disease-related mutations related to deposition of the peptide into the vascular system showed that fibrillar structures of the peptide assume a structure that deviates from the wild type morphology of which the contribution to disease have yet to be determined (4). From these examples and other investigations into this topic we concluded that the complexity of the amyloid beta peptide mixture should be acknowledged upon investigating the contribution of this peptide toward disease and development of potential therapeutic developments. During my talk, I will provide an overview of our recent work on complex amyloid beta peptide mixtures and their potential contribution toward progress of Alzheimer disease.

Speaker
Biography:

Hélène Castel started to develop different variants of the electrophysiological technique at the university of Rouen in the laboratory of Dr Vaudry (U413 Inserm) and biochemical approaches to give a comprehensive view of modulation of the GABAA receptor-channel function by interacting proteins. She received her PhD in Neurosciences, Molecular and Cell Biology at the Rouen University in 2000, and then spent 2 years on a post-doctoral position in Pr Colquhoun’s laboratory at University College of London, UK. There, she has developed fast-concentration-jump techniques to mimic electrical fast synaptic inputs on recombinant NMDA receptors and acquired expertise in molecular biology through mutagenesis of NMDA receptor subunits. In 2002, she obtained a permanent position as chargée de Recherche (CR) at the French National Institute of Health (Inserm) and University of Rouen. In 2010, she became group Leader “Astrocyte and Vascular Niche” and since 2015, she is co-head of the international platform “Cancer and Cognition” under the French North-West Canceropole. She develops projects based on vasoactive and chemokine G protein-coupled receptors (GPCRs) in tumor brain, brain vascular physiopathology and on cognitive dysfunctions induced by cancer and targeted therapies.

Abstract:

Subarachnoid haemorrhage (SAH) refers to extravasation of blood into the compartment between the brain and the tissue that covers the brain. This is often due to a ruptured aneurysm and accounts for up to 5% of all new stroke cases. Survivors of SAH commonly experience sequels that affect their day-to-day lives and which could persist years after; these include fatigue, memory deficits, executive function, language, depression and sleep disorders. The cerebral arterial vasospasm (CV) is a complication of the SAH, and may by associated with neurological deficits, microthrombosis and cerebral ischemia. Despite advances in diagnosis and surgical treatment, effective therapies are still limited and clinical outcomes remain disappointing. The CV may be due to vasoactive peptides which are released locally and which, under normal conditions, control the blood/brain exchange. One of the most potent vasoactive peptides is urotensin II (UII). Urotensin II (UII) and its paralog URP activate a G protein coupled receptor (GPCR) named UT. UII exerts a wide range of physiological effects and regulate the endocrine, cardiovascular, kidney and immune functions. Our study aimed at providing significant advances and proof of concept of a new therapeutic target in SAH in a major area of public health involving neurological disability and the dramatic change in the quality of life. We led a single-center prospective study over a period of 24 months, including all patients with SAH of aneurysmal origin with external ventricular bypass and aneurysm exclusion, classified stage 1 or 2 in the WFNS scale. Blood and CSF samples were collected from D0 to D8. The ROC curve showed that the plasma concentration of UII is a discriminating factor for the occurrence of CV (AUC 0.824, P = 0.02, patent FR1356995, 2013). A mouse model of SAH was also developed via a double injection of arterial blood into the magna cisterna during two consecutive days. Occurrence of CV of the cerebral middle, basilar and anterior arteries and a number deposition of fibrin (microthrombis) were observed from the 2nd to the 14th day post-SAH, as well as increase in the activity of caspase-3 from Day 3 to 14 in brain cortex, hippocampus, endothelium and choroid plexus. Impaired sensorimotor functions (beam walking test) were detected from D7 to D10. Then, we investigated the impact of the UII system in this SAH model my means of wild-type (UT+/+) and KO-UT (UT-/-) mice. UT-/- mice do not exhibit any remarkable phenotype. The β-galactosidase activity (reporter of the UT transcription) was very faint in the brain cortex, endothelium, and choroid plexus in Sham UT-/- mice and strong in brain cortex, hippocampus, choroid plexus and microvessels 10 days post-SAH. Consistent with these observations, we demonstrated the expression of UII peptide in the brain cortex, the hippocampus and in some large and small arteries only in SAH mice. Interestingly, the UT ligand urantide, listed so far as \"antagonist\", but now definitively characterized as a biased ligand1, completely prevented CV, microthrombosis and consecutive neurosensitivomotor deficits in SAH mice, suggesting that UT ligands may constitute interesting therapeutic tools. We should in the future, explore the effect of other UT biased ligands which may cross the blood brain barrier and bind UT, mainly expressed during the course of the SAH pathology. These compounds with minimal side effects can be extremely innovative in the treatment of SAH, but also in other cardiovascular pathologies.

Speaker
Biography:

Mehrdad Shamloo has completed his PhD from University of Lund, Sweden. Since the inception of his doctoral studies in 1999, he has been working in the field of neuropharmacology and drug discovery and has led numerous industrial and NIH funded research projects in this field. Currently, he is Associate Professor of Neurosurgery and director of Behavioral and Functional Neuroscience Laboratory at Stanford University School of Medicine. He directs multiple preclinical and pharmacological drug discovery program with special focus on neuroprotective compounds, cognitive enhancers, and regenerative small molecules.

Abstract:

Despite a huge impact on both individuals and public health, Alzheimer\'s disease (AD) remains incurable without an effective, disease-modifying therapy. The lack of effective therapy in AD is attributable to the complex array of factors that are involved in its development and progression. β1-adrenergic receptor (β1-ADR) is promising neuropharmacological target for the treatment of AD. Dysfunction of β1-ADR and its downstream signaling cascade are strongly implicated in cognitive symptoms of AD. Besides its involvement in cognitive symptoms, deficiency of the endogenous ligand for β1-ADR, noradrenaline, is highly correlated with several pathological features of AD including tissue load of amyloid plaques and neurofibrillary tangles. The involvement of β1-ADR in multiple key aspects of AD is a unique and therapeutically attractive feature that could enable a comprehensive strategy toward the treatment and management of the disease. Importantly, recent studies from our laboratory have shown that stimulation of β1-ADR is a promising therapeutic strategy for AD. In two independent preclinical models of AD, we have shown that stimulation of β1-ADR with the partial agonist, xamoterol, restores the cognitive deficits associated with the disease. Moreover, the β1-ADR agonist xamoterol increases the microglia phagocytic activity as evident by increase in CD68 and reduces soluble form of amyloid beta peptide (AB1-40). These data suggest that pharmacological modulation of β1-ADR could provide a novel therapeutic strategy to provide comprehensive therapeutic benefit for AD by simultaneously addressing cognitive symptoms and underlying neuropathology.

Break: Networking & Refreshment Break 10:30-11:00 @ Orwells Restaurant
Speaker
Biography:

Amir Mufaddel has graduated from Khartoum University and had his MD in psychiatry from Sudan Medical Specialization Board in 2008. Currently working in AlAin hospital, Community Mental Health Services. He is an adjunct lecturer in United Arab Emirates University. He has published several papers in reputed journals mostly reflecting the psychiatric aspects of physical conditions such as neurology, infectious diseases and dermatology.

Abstract:

Background: Central nervous system (CNS) calcifications can occur in a wide range of conditions with different etiologies. Calcifications can occur as physiologic, dystrophic, congenital or vascular calcifications. Methods: The aim of this paper was to discuss differential diagnosis of psychiatric conditions associated with CNS calcifications. A literature review was conducted using the key words cerebral calcifications, basal ganglia calcifications, intraaxial calcifications, extra-axial calcifications and psychiatric symptoms. Type, duration, and course of psychiatric symptoms were reviewed. Results: Brain calcifications can occur as intra- or extra-axial calcifications. Structures commonly involved in intra-axial clarifications are the basal ganglia and the cerebellum. Calcifications can be idiopathic/genetic such as that occurring in Fahr’s disease. Psychiatric symptoms in individuals with basal ganglia calcifications can present with variable clinical features including cognitive decline, auditory hallucinations, delusions, irritability, aggression, depressed mood, anxiety, personality changes and suicidal thoughts. Psychiatric symptoms can be acute or chronic; and some patients received clinical psychiatric diagnoses including: dementia, schizophrenia-like psychosis, mood disorders, frontal lobe syndrome, and mental retardation. Extra-axial calcifications such as that occurring in falx cerebri and the pineal gland can also be associated with psychiatric symptoms. Rare conditions with falx cerebri calcifications such as Gorlin-Goltz syndrome can present with acute course or with relapses and remissions. Conclusion: Radiologic investigations are useful tools to exclude organic pathology in patients presenting with psychiatric symptoms. For psychiatric patients who present with CNS calcifications, the location of calcification and the clinical psychiatric and systemic presentation are of vital importance in diagnosis.

Shahid Hussain Sheikh

NIDS Treatment & Research Center, Pakistan

Title: Neurological disorders in children / the sheikh’s syndrome

Time : 11:20-11:40

Biography:

Shahid Hussain Sheikh graduated his MBBS in 1980 and Ph.D. in Neurology in 2011. He served in various medical research positions at the Univ. of WA Med. Cntr. from 1982 to 1992. As a Professor of clinical Physiology in 1992 at American College of Prof. Edu., also served A.C. Med. Cntr, as a Research Scientist/ teaching faculty and clinical studies. He has pioneered unveiling of the proliferating viral RNA based clinical pathology of the affected nucleus of the controlling neurons.

Abstract:

The label of “Cerebral Palsy” has been used frivolously due to the lack of knowledge of the Brain’s pathology. Since 2004, a number of researchers have stumbled upon a new paradigm in the field of Neurology1 that now opens up a new door of hope to better the quality of life of the suffering infants, children and adolescence worldwide. Now, many children with CP are known to be suffering from the Neuronal Sub-Nucleus Neuro viral RNA proliferation that begins as early as the inception of a new baby. The genetically transforming diseases now take a back seat to this new revelation, where, the Neuro Viral RNA’s being part of the chromosomal DNA of the sperm or the Ovum also ready to proliferate in the developmental stage of the Neuro Disk of the fetus in the first trimester. Therefore, the brain, spinal cord and all nerves may have the greater architectural influence of the Neuro Viral RNA Proliferation. So much so that, this influence may be carried out in to the developing functions of the organelles, cells, membranes, tissues, organs, systems. All cells, membranes, tissues, organs and systems are constructed with the Sensory Nerves and Motor Nerves, therefore, connected and controlled by the peripheral and central nervous system. On the other hand, maternal Immunity interferes in the defense, so long to protect the developmental anomalies, equal to the potency of the hosting mother’s immunity. If the virion / RNA proliferation is faster than the production and potency of the immune cells, of course, the battle is going to be lost. Baby is going to be presenting the pregnancy related challenges, and if born, may have some serious developmental challenges. Any Neuronal anomaly among the billions of developing neurons will translate in to what we know today as the Cerebral Palsy, Late Milestone, Autism, Hydrocephaly etc. It is now discovered that Neuro Viral RNA proliferation does take place due to the auto immune disorder, in particular, the Neuro Immune Dysfunction Syndrome now further defined as “Sheikh’s Syndrome” (A Multi Neuronal Sub-Nucleus Neuro Viral RNA Proliferation).

Wail M Hassan

University of Wisconsin-Milwaukee, USA

Title: Gene expression changes triggered by amyloid beta toxicity

Time : 11:40-12:00

Speaker
Biography:

Wail M Hassan has completed his Bachelor’s degree in Microbiology and a Graduate Diploma in Public Health from Alexandria University in 1990 and 1993 respectively. He has completed his PhD in Microbiology from the University of Southern Mississippi in 2004. He has occupied several Post-doctoral positions between 2004 and 2010 at University of Colorado at Boulder, the National Naval Medical Center and University of Nebraska Medical Center. In 2011, he joined the University of Wisconsin-Milwaukee as an Assistant Professor where he continues his research focusing on the molecular mechanisms of amyloid beta toxicity.

Abstract:

Multiple genes have been linked to Alzheimer’s disease (AD) implicating multiple metabolic pathways in its pathogenesis. It is not clear, however which of these genes are involved in general stress response and which are linked to AD-specific pathologies. To make an attempt to answer this question, we investigated changes in gene expression induced by human β-amyloid peptide (Aβ) in a transgenic C. elegans Alzheimer’s disease model. Aβ-induced gene expression changes were compared to those caused by a synthetic aggregating protein to identify Aβ-specific genes. Among the Aβ-specific genes identified in this study were genes involved in aging, lifespan regulation, proteasome structure and function and mitochondrial function. Interestingly, a significant overlap between Aβ- and Cry5B (a bacterial pore-forming toxin) induced gene expression alterations was observed. Further testing suggested the involvement of membrane damage in Aβ pathogenesis. In this study, we segregated Aβ-specific gene expression changes from general stress response in a simple metazoan animal and provide evidence implicating membrane damage in Aβ toxicity. We hope this work will eventually help identify novel therapeutic targets and further our understanding of AD pathogenesis.

  • Young Researcher Forum
Location: Guggenheim Room

Session Introduction

Reeta Jaya Philip

Dr. S. R. Chandrasekhar Institute of Speech and Hearing, India

Title: Test battery approach to cognitive communication disorders in traumatic brain injury

Time : 12:00-12:20

Speaker
Biography:

Reeta Jaya Philip is a PhD scholar in Speech Language Pathology at Dr. S R Chandrasekhar Institute of Speech and Hearing, Bangalore University, India. Her area of research interest includes traumatic brain injury and related disorders and adult neurogenic language disorders.

Abstract:

Background: Traumatic brain injury (TBI) can have a major impact on an individual’s cognitive, social, physical, emotional and behavioral aspects. Management of Cognitive Communication Disorders (CCD) in individuals following traumatic brain injury is a clinical challenge. Aim: To highlight the use of test battery approach in substantiating the nature and severity of cognitive communication disorder subsequent to TBI. Method: The participant of this study is a 20 year old male who experienced traumatic brain injury due to road traffic accident. MRI revealed contusions in bilateral inferior frontal lobes. Neurosurgical management was bicoronal skin incision and bifrontal decompressive craniotomy. Participant underwent various neuro surgical procedures such as Bifrontal craniotomy and bilateral fronto-parietal craniotomy. The diagnostic test battery incorporated for the assessment was Mini Mental Status Examination, Addenbrook’s Cognitive Examination-Revised, Brief Test of Head Injury, Bililingual Aphasia Test. Results: Cognitive linguistic deficits were explored by using the test battery. Results revealed severe deficits in auditory comprehension, expression, attention, orientation, visuospatial functions, memory and problem solving. Code mixing and translation disorder was also seen in cross linguistic examination. Conclusion: Study highlighted the cognitive communication disorders in TBI. Clinical evaluations and neuro linguistic correlations were done. The results revealed the utility of test battery approach in exploring the complete nature of CCD in TBI. Results have implications for cognitive linguistic rehabilitation of TBI.

Speaker
Biography:

Daly Sebastian is currently working as a junior Lecturer in Department of Speech Language Studies, Dr. S. R. Chandrasekhar Institute of Speech and Hearing, Bangalore University. Her areas of research interest are neurogenic communication disorders, Multilingualism and neuro cognition. She has published papers in reputed journals and contributed chapter in International text books.

Abstract:

Introduction: Aphasia defined as a multimodal loss of language is one of the most feared symptoms of stroke. About 21– 38% of acute stroke survivors suffer from aphasia. Boca’s aphasia is a classical form of expressive aphasia. Preserved auditory comprehension, impaired repetition, nonfluent speech and lesion in the foot of the third frontal convolution (Broca’s area, Broadmann’s no. 44) are classical features of Broca’s aphasia. Aim: (1) To investigate the relationship between phonological paraphasia and auditory temporal processing deficits in persons with Brocas’s Aphasia. (2) To investigate the role of auditory temporal training for the treatment of phonological paraphasia in persons with Bocas aphasia. Method: Participants: Twenty participants with a history of ischemic stroke in the left Middle Cerebral Artery and clinically diagnosed as Brocas Aphasia were selected for the study. Twenty participants were divided into two group based on their neurolinguistic features. There were a group of 10 aphasics with semanatic paraphasia and the other 10 with phonological paraphasia. Informed consent was taken from the participants and all the procedure were strictly adhered to ethical guidelines. Stimuli: Auditory temporal processing testing was carried out using a maximum likelihood procedure toolbox, which implements an MLP in MATLAB software. The participant’s ability to detect a temporal gap in the center of a 750 msec broadband noise was measured. The noise had 0.5 msec cosine ramps at the beginning and end of the gap. In a two-interval alternate forced choice protocol was used. Phase 1: Psycho acoustic evaluation of temporal processing was done by estimating gap detection threshold (GDT). Comparison was done between the semantic paraphasia group and phonological paraphasia group. GDT of both the groups were compared with the normal age matched subjects thresholds (which was obtained for the purpose of another study). Phase 2: Phonological paraphasia group was divided into two, group A and B with five participants in each group. Group A was taken as control group and Group B was taken as experimental group. Group B was given 15 hours of auditory temporal based cue training which included speech and non-speech stimuli with difference only in durational aspects. After 15 sessions of training group A and B were tested by using Gap detection test and percentage of phonological paraphasia was also calculated. Results: There was significant difference in the GDT scores of phonological paraphasia group and semantic paraphasia group (P<0.05). Phonological paraphasia group had poor GDT scores on the right ear which is opposite to the site of lesion. However, semantic paraphasia group had values similar to the normal participants. Within group investigation of temporal cue based training indicated that there were no substantial changes in GDT and percentage of phonological paraphasia (POP) of group A. However, GDT became improved for group B and POP was also reduced. Improved temporal resolution was seen in the right ear responses of Group B. Discussion: Our findings are emphasizing the need for viewing the deficits and rehabilitation options of persons with Brocasapahasia slightly different from a conventional view. Study give insight into the need for temporal cue based assessment and treatment options for persons with Broca’s Aphasia. The reason for the poor GDT of phonological paraphasia group was tried to explain based on the nature of site of lesion and recent evidences in the role of Brocas area in speech perception. Supporting evidences were taken from current models of brain language processing claim that several temporal, parietal and frontal areas interact in order to deliver the many features of language ability. Results were also supported by experience dependent neuroplasticity based research in aphasia. Current study attempted to highlight the need for translational research in aphasia also. The study will serve as a contemporary perspective in Aphasiology.

Break: Lunch Break 12:40-13:20 @ Orwells Restaurant
  • Poster Presentations @ 13:30-14:30
Location: Guggenheim Room