24^th International Conference on Neuroscience and Neurochemistry July 23-24, 2018 Birmingham, UK

Lauren Quesenberry is a second-year student in the Clinical Mental Health Counseling Program at The Chicago School of Professional Psychology, Washington DC. She obtained a Master of Arts in Women’s Studies Gender Studies from Loyola University Chicago in 2011 and a Bachelor of Arts in English and Minor in Psychology from Gardner-Webb University in 2009. Her areas of professional and academic focus include women’s trauma/recovery and LGBTQ populations.

This poster session focuses on a study of the identity formation of three specific lesbian/bisexual women who were raised in the Southeast region of the United States characterized by a strong Christian fundamentalist/evangelical influence. Narrowing in on the intersection between religion, sexual orientation, geographic region and/or culture (amidst a variety of other factors having to do with the personal lives of these three participants), this poster will highlight therapeutic implications for counselors and psychologists. Beginning with the basics of identity politics and theory, intersectionality is a concept coined by Crenshaw (1989) to describe the way that issues like racism, sexism etc. seem to overlap and create multiple levels of social injustices. Research findings suggest that each minority class a person possesses compounds and interacts, thereby increasing threats of discrimination. This conceptualization of identity formation challenges the hierarchal nature of power within society and provides the following implications for psychological practitioners: practitioner cultural competence is a dire necessity. When working with persons who are participants in one or more minority classes, the following frameworks must be integral to the counseling process: feminist theory, multicultural counseling theory, relational-cultural theory etc. (i.e. empowerment modality used to dismantle the ways in which an individual has been silenced or blamed for his/her sexual orientation as “choice,” etc.). Understand the dangers of prioritizing culture over other factors/identities (sexuality, SES, etc.) which may reinstate powerlessness (i.e. lack of access to services, problems within that culture).

Mariannina Amato graduated in Psychology and specialized in Psychotherapy. She is an ASPIC-APA member. She currently works in the Child Neuropsychiatry of the ASP-CZ. She graduated in Psychology at the Sapienza of Rome in 1990, specialized in Clinical Psychology of Community and Integrated Humanistic Psychotherapy in ASPIC School in Rome in 2003. She attended the Master in Health Management 2014, the courses of Psychodiagnostics and Family Mediation in 1998. She expert in child psychology, problems of sexual abuse, foster care and family mediation at the Court of Lamezia Terme and Catanzaro from 1998 to today. Since 2007 she work as Psychologist and Psychotherapist at the OU of Obstetrics Gynecology. Currently she work as a psychologist in the Child Neuropsychiatry of Lamezia Terme, Italy.

The latest research in the field of neurosciences on empathy, tuning, emotional understanding and high executive functions found in 3D therapy is an effective implementation. 3D therapy applies the 3D printer in the realization of 3D objects that will be therapeutic elements. The 3D object is the result of emotional involvement in the therapeutic session. The evoked dysfunctional emotion is transposed as a graphic on a sheet by the same child. The method has a sequential process that is activated with adequate visual and verbal stimulation (phase A) the child's emotional involvement and blocked emotion that causes discomfort. The emotion evoked, transposed on a graph, is materialized in a 3D object (phase Bx) placed in front of the child. The observation of the object unleashes in the child (phase Cx), a strong emotional impact that goes from amazement/ wonder to surprise/novelty, an impact that calls for a dynamic process of visual and tactile observation (phase D). It follows a comparison and narration, with a continuous search for solution to the problem (phase E), up to the understanding and emotional stabilization (phase F) with the assimilation of new information on one's self, made more and more cohesive and integrated. The observation process involves the activation of mirror neurons that reflect the objective emotions, made clear and real by the 3D object, and the executive functions that plan a research strategy and solution to understand and integrate the emotional elements producing a real change in the self of the child.

Nibras Rothwell is a PhD student in Psychology Department at University of Bolton. She is interested in Psychology, Neuropsychology, Neurocognition, Educational Psychology and Human Memory in general. She has completed professional academic degrees in teaching, interpreting and translation, British airlines experience, case working, leadership, advice, advisory, a quality and assurance assessment, and English law interpretation. She has been living, communicating and working in various countries and has gained excellent experience. Her educational background and experiences made her ambitious to investigate more aspects in human brain, cognitive abilities, performance and behaviour

Previous research has shown that younger adults often perform better than older adults on tests of cognitive function including those of memory, attention, and executive function. However, there has been less research that has investigated the differences between younger and middle aged adults, especially those currently in education. This study aimed to bridge this gap. A group of 20 younger students (aged between 19 and 25) was compared to a group of 20 middle-aged learners (aged between 35 and 55). Both groups were required to complete a selection of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). In addition, both groups were required to complete five standardised questionnaires that measured further aspects of cognition and behaviour, including resilience and self-esteem. In terms of the CANTAB tests the younger group generally outperformed the middle-aged group, although not significantly. However, in of one of the more complex executive function tasks, a test of multitasking, the middle-aged group seemed to have particular difficulties responding accurately to conflicting stimuli and multiple significant differences were found. In terms of the behavioural measures, the younger participants scored significantly higher on self-esteem, but middle-aged participants had significantly higher scores on the BUSS measure of academic tenacity and on the CD-Risc and Resilience Scale. While this was a small pilot study, it does suggest that there may be genuine differences between younger and middle aged students in certain aspects of cognition and behaviour that warrant further exploration.

Francesca Sardina is interested in the study of DNA damage response during neuronal development and carcinogenesis. In this last years, she started to characterize the role of HIPK2, a kinase controlling DNA damage and cytokinesis, in the regulation of spastin protein closely involved in Hereditary spastic paraplegia, a neurodegenerative disease. Her studies could open the way to develop new and innovative therapeutic approaches in the field of neurodegenerative diseases.

The alteration of axonal-transport is an early and causal event in many neurodegenerative diseases (ND). Among the mechanisms contributing to axonal-transport defects, the loss of microtubules dynamism is one of the key mechanisms. Spastin is a microtubule severing protein involved in cytokinesis and in axonal-transport. Mutations in SPG4 gene encoding spastin are found in patients with hereditary spastic paraplegia (HSP), an autosomal dominant ND. Recently, it has been shown that to increase spastin levels rescues the pathological phenotypes in HSP-patient-derived cells suggesting that intervening to modulate spastin levels may be a valid therapeutic strategy in ND characterized by spastin misregulation. We found that spastin is regulated by the kinase HIPK2 in neural compartment. HIPK2 depletion leads to spastin down regulation in a proteasome-dependent manner and impairs axonal-transport. Wild-type-HIPK2 overexpression, but not kinase-defective- HIPK2, increases spastin levels and rescues axonal transport defects in spastin-deficient motor neurons. Mechanistically, we showed that HIPK2 phosphorylates spastin at S268. This phosphorylation stabilizes spastin and prevents its polyubiquitination and proteasome degradation. These results, in addition to expanding our understanding of the HIPK2/spastin axis in neural compartment, might provide the basis for the development of a new therapeutic approach to treat HSP.

Imane Ghafir El Idrissi is a third year PhD student in Pharmaceutical and Medical Biomolecular Sciences at the University of Bari, Italy. Her thesis is entitled as “Role of Prion protein and Involvement of metal ions in the onset of Alzheimer’s disease”. On 5th February 2018, she has been awarded with a scholarship in the call for PhD mobility for study/research at University of Sheffield (UK) within the framework of the GLOBAL-DOC project. From October 2014 to September 2018, she is involved in a Marie Skłodowska-Curie Action: Industry Academia Partnerships and Pathways (IAPP) Grant Agreement 612347 title D3i4AD and she spent one year in Sheffield (UK), from October 2015 to March 2016 and from November 2016 to June 2017, during which she developed a cell-based assay, by using HEK 293 cells, useful for a high-throughput screening of small molecules able to disrupt the binding of Aβ1-42 to PrPC, under the supervision of Prof Beining Chen and Prof Nicola Antonio Colabufo.

Alzheimer’s disease (AD) is characterized by a severe loss of memory function. It has been proposed that AD associated memory loss is caused by soluble amyloid-beta oligomers (OS), especially during early stages of AD before significant neuronal cell death has occurred. It has been shown that PrPC mediates the toxic effect of Aβ oligomers and is required for Aβ oligomer-induced suppression of synaptic plasticity, synapse damage, and neuronal cell death Aβos binding to PrPC results in Fyn activation which leads to NR2B subunit of NMDARs phosphorylation and in tau hyperphosphorylation, the second pathological hallmarks of AD. Treatment with PrPC antibodies against the Aβ oligomer binding site prevents the inhibition of long-term potentiation and reverses cognitive deficits in AD transgenic mice. Copper ion (Cu2+) is another important plyer in this scenario. In fact, the PrPC in its copper-loaded state binds to the NMDAR complex to allosterically reduce its glycine affinity, thereby increasing desensitization. When copper is chelated (i.e., by BCS or monomeric Aβ1–42) or when PrPC is absent or functionally compromised (by GPI anchor cleavage or binding to Aβ oligomers), glycine affinity is enhanced, reducing receptor desensitization and producing pathologically large, steady-state currents that contribute to neuronal damage. There has been considerable interest in identification of compounds that bind to PrPC, stabilizing its native fold and thereby acting as pharmacological chaperones to block prion propagation and pathogenesis. However, compounds binding PrPC could also inhibit the binding of toxic species and may have a role in treating AD. The work outlined here details investigations into a group of around 100 compounds. These were screened in HEK 293 and N2a differentiate cells, wild type expressing PrPC in order to establish and optimize their in vitro ability to disrupt Aβ1-42-PrPC binding, establish their structure-activity relationship and identify a lead compound.

Muhammad Imran Naseer joined the CEGMR as a Neuroscientist from Gyeongsang National University, South Korea. His area of expertise includes molecular, cellular and developmental neuroscience. His PhD work was based on the effect of ethanol on siRNA-Mediated GABAB1 receptor expression for downstream signaling pathways, apoptotic neurodegeneration, maternal epileptic seizure and role of GABAB1 receptor expression in early development of pre and postnatal rat brain. Currently, he is involved in neurogenetic research program at CEGMR working on common neurologic disorders including Progressive Myoclonic, Juvenile Myoclonic, Idiopathic Generalized Epilepsy, microcephaly and other neurodegenerative and neurodevelopmental disorders in the western region of Saudi Arabia using microarray platform for array CGH, CNV/SNP analysis and next generation for expression and whole exome sequencing analysis. Further aim is to study the role of GABAB receptors and KIFs genes in early neurological defects related to neurodegenerative disorders in the Saudi Arabia including epilepsy, microcephaly, Alzheimer's and mental retardation.

Wiedemann–Steiner syndrome (WSS) is an autosomal dominant disorder characterized by short stature, hypertrichosis, intellectual disability, developmental delay, along with facial dysmorphism. KMT2A gene (OMIM: 159555) is one of the known genes that are responsible for WSS and still new phenotypic features continue to be added in this conditions. Here in this study we report a novel compound heterozygous c.2017G>C (p.Ala673Pro) in exon 3 and c.3180G>T (p.Glu1060Asp), mutations in exon 4 of the KMT2A gene in two affected girls in Saudi family with microcephaly, speech disorders, walking difficulty and intellectual disability. Whole exome sequencing (WES) results showed two rare, missense variants in compound heterozygous state in the KMT2A gene in these two affected girls whereas the both the parents were heterozygous. A compound heterozygous c.2017G>C in exon 3 and c.3180G>T in exon 4 of the KMT2A mutation confirm the typical WSS phenotype. Furthermore, the WES results were validated by using the Sanger sequencing analysis in affected and parents along with 100 unrelated control from normal population. Our results showed similar type of genotype and phenotype of the patient is compared with the earlier reported patients in the literature, in an attempt to broaden our knowledge of this rare syndrome.

Odeya Damri is in her last year of PhD in Ben Gurion University. Her research is focusing on psychiatric disorders, in general, and bipolar, in particular. During her MSc she published two articles which focusing on understanding the mechanism of lithium in mice model. With the guidance of the supervisor, the prof. Galila Agam, she attempts to establish a model for manic depression in mice based on mitochondrial minor injury while examining weather ROS scavengers or autophagy enhancers alleviate mitochondrial changes. In addition to that she is teaching biochemistry for the fifth year.

Mitochondrial-function is at the nexus of pathways regulating synaptic-plasticity and cellular resilience. The involvement of brain mitochondrial-dysfunction along with increased reactive oxygen species (ROS) levels, accumulating mtDNA mutations and attenuated autophagy are implicated in psychiatric and neurodegenerative diseases. We aimed to model mild mitochondrial-dysfunction assumed to occur in bipolar-disorder (BPD) using exposure of human neuronal cells (SHSY5Y) to rotenone (an inhibitor of mitochondrial-respiration complex-I) and to find out whether ROS scavengers and/or autophagy enhancers can ameliorate neuronal mild mitochondrial-dysfunction. Incubation with an extremely low rotenone dose (10 pM) for 72 and 96 hours did not affect cell viability but induced a dual effect on mitochondrial-respiration. Exposure for 72 hours induced an overshooting several-fold increase in basal, maximal and ATP-linked oxygen-consumption-rate (OCR) but not in non-mitochondrial OCR while exposure for 96 hours significantly decreased all OCR parameters. The autophagy enhancers lithium, trehalose, rapamycin and resveratrol added for the last 24 of the 72 hours exposure to rotenone counteracted rotenone`s effect on OCR parameters. Only lithium added for the last 48 of the 96 hours exposure to rotenone reversed rotenone’s effect on OCR parameters. The effect of 10 pM rotenone mimics BPD studies in which neuronal cell death is not discerned despite reproducible reports of mitochondrial-dysfunction. The enhancing effect of the low dose of rotenone on mitochondrial-respiration parameters is interpretable as the cells compensatory response to the very mild mitochondrial-dysfunction. Our regime differs from the rotenone-induced Parkinson’s model (10 pM vs. at least 10 nM) by not affecting ROS levels nor cell viability but reducing most OCR parameters following 96 hours of exposure. The effect of lithium reversing rotenone’s effect on OCR parameters is compatible with lithium’s known positive effects on mitochondrial-function, in general, and oxidative phosphorylation complexes, in particular.

Serena Asslih is an MSc student at Ben-Gurion University, Israel. She carries out a behavioral and molecular research project aiming at mimicking mitochondrial dysfunction robustly reported in bipolar disorder under Prof Galila Agam's mentorship. In parallel, to achieve knowledge and practice in the preclinical world, which is her central interest, she took upon herself shift duties in hospital laboratories.

Despite the high prevalence (~1% of the adult population) of bipolar-disorder its pathophysiology or the mechanism by which effective medications exert their therapeutic effect has not yet been unraveled but data from other groups and ours indicate brain mitochondrial dysfunction in the patients and beneficial effects of mood stabilizers (anti-bipolar drugs) on mitochondrial function. We therefore aim to model mild mitochondrial dysfunction in mice using the oxidative phosphorylation (OxPhos) complex I inhibitor, rotenone, to induce affective-like behavior. Adult ICR mice were treated daily with 0.25, 0.5, 0.75, 1.2 and1.5 mg/kg/day rotenone for four, six and eight weeks following which the mice were subjected to a battery of behavioral tests [open field, elevated plus maze (EPM), sweet-solution (saccharin) preference (SSP), rotarod, forced-swim test (FST) and amphetamine-induced hyperactivity] and neurochemical assays. Chronic administration of all rotenone doses for four weeks did not affect spontaneous activity or time spent in the center of the open field, SSP or behavior in the EPM. 0.5 mg/kg/day for four weeks induced a trend for attenuation of amphetamine-induced hyperactivity. 0.75 mg/kg/day for four or six weeks reduced the immobility time in the FST and protein levels of all mitochondrial respiration complexes except for complex IV in the hippocampus with an inverse effect in the frontal-cortex. As for mitochondrial-respiration – there was a trend for upregulation in the hippocampus and down regulation in the frontal-cortex. Eight weeks of treatment significantly increased the immobility-time and reduced mitochondrial -respiration without affecting protein levels of LC-3II and mitochondrial-respiration complexes. In conclusion, 0.75 mg/kg/day rotenone exhibited dichotomial effect on depressive-like behavior reminiscent of bipolarity. We are currently investigating whether Reactive Oxygen-Species (ROS)-scavengers and/or autophagy enhancers rescue the bipolar-like behavior and neurochemical markers.