Biography:

Abstract:

Several studies have indicated that abnormal prenatal changes in the circulating glucocorticoids (GCs), induced by either maternal stress or exogenous GC administration, significantly alter the development of Purkinje cell (PC) dendrites and synaptogenesis. However, it is unknown whether a single course of a therapeutic dose prenatally GCs alters the major synaptic vesicle protein synaptophysin (Syn). Thus, in this study we analysed whether a single course of prenatally administered betamethasone phosphate (BET) in pregnant rats changes the immunohistochemical expression of Syn along with locomotor behaviour (rota rod-test). The data obtained showed that in utero BET exposure resulted in a significant immunohistochemical underexpression of Syn and a significant reduction in locomotor behaviour during late postnatal life. In conclusion, our previous and current works indicate that prenatal BET administration significantly modify the cerebellar development. Of note, these and other experimental data do not portend to minimize the beneficial effects of BET administration when there is a risk of respiratory distress/bronchopulmonary dysplasia in preterm infants.

Biography:

Abstract:

Intellectual disability is seen in up to 1% to 3% of the general population, and is often dichotomized into syn- dromic and nonsyndromic forms.1 A genetic aetiology accounts for about 25% to 50% of cases, with up to 700 monogenic mutations identified so far.2 Recent advances in genetic testing have allowed the identification of an ever- increasing repertoire of genes causing intellectual disabil- ity.2 Characterization of their protein products has shed light onto the diverse biological pathways affected in this important neurological disease that results in significant impairment in cognitive and adaptive behaviour, and which has important medical and social implications.3 Aberrancies in synaptic vesicular transport and intracel- lular protein trafficking have been highlighted among the various biological pathways reported to cause intellectual disability.3 Included in these are mutations in genes coding for Rab proteins (rabaptins), a group of small Ras GTPases that have been shown to play an important role at different levels of the cellular trafficking pathway.4–6 Although over 60 Rab proteins have been identified so far, only a few have been implicated in human disease, including in patients with intellectual disability with or without associ- ated brain malformations.7,8 RUSC2, officially known as RUN and SH3 domain con- taining-2, is a gene found on chromosome 9p13.3 (gene identifier [ID] 9853, Mendelian Inheritance in Man [MIM] 611053). RUSC2 codes for iporin, a ubiquitous protein with moderate to high expression in the human brain.9,10 The literature on the functions of iporin remains sparse, but there is some evidence that it interacts with Rab1b and Rab1-binding protein GM130,10 both of which are also expressed in the brain, with highest expression in dendritic spines where they appear to play an important role in synaptogenesis.11 So far, no mutations in RUSC2 have ever been shown to cause human disease, and no animal models disrupting this gene have been described. However, to our knowledge for the first time, we describe the clinical presentations of three patients (two male siblings and one unrelated female) with severe intellectual disability and microcephaly. Through wholeexome sequencing, all three were found to have inherited homozygous nonsense mutations in RUSC2. This report adds to the expanding landscape of genetic causes of intellectual disability, and suggests that RUSC2, probably through its interactions with Rab proteins and their effector molecules, may play an important role.

Biography:

Abstract:

The axons of embryonic brain, spinal cord and retina extend along the extracellular voltage gradient towards the cathode in a process known as galvanotropism. In embryonic nervous tissues, positive direct current (DC) potentials are generated by neuroepithelial cell’s sodium transport, of which disruption results in erroneous axon path-finding, suggesting that electric fields play a pivotal role in orienting newborn axons. However, the experimental evidence was lacking for the cell surface molecule that is activated asymmetrically in an electric field. Here, it is shown that integrin activation mediates electric axon guidance. Retinal strips of chick embryos were embedded in Matrigel®, and cultured in the electric field of the same strength as that in vivo (15 mV/mm). Matrigel® contained the same extracellular matrix proteins as in the embryonic retina, laminin and collagen, to which integrins bind. Retinal ganglion cell axons extended towards the cathode. A monoclonal anti-chicken integrin antibody (TASC), which enhances integrin-ligand binding, accelerated the cathodal growth. A reduction in the extracellular free Ca2+with EGTA also enhanced the cathodal growth, which suggested that millimolar Ca2+ inhibited axon growth, and also that the influx of Ca2+ was unlikely to be essential for cathodal steering. In the presence of Mn2+, which non-specifically activates integrin-ligand binding, the axons formed local meshes. These results suggested that the inhibition of integrins by the extracellular Ca2+ underlies electric axon guidance.

Biography:

Abstract:

Biography:

Si Ching Lim has a special interest in Dementia Care particularly in patients with behavioural and psychological symptoms of dementia. She is currently in charge of a 20 bedded Dementia Ward and is responsible in developing the ward and training the staff in managing elderly with delirium and dementia with challenging behaviors. Current projects involve seeing surgical patients with delirium and dementia post operatively and educating surgical nurses management of BPSD. She is also an Adjunct Assistant Professor at the National University of Singapore and Dukes Graduate Medical School.

Abstract:

Dementia is becoming an expensive disease worldwide and its prevalence is on the rise, particularly in the developing countries. The non-cognitive symptoms of dementia, also known as neuropsychiatric symptoms or behavioural and psychological symptoms of dementia (BPSD) is particularly challenging for the caregivers resulting in significant caregiver stress, leading to burnout and institutionalization. BPSD occurs in >90% of people with dementia at some point during the course of their illness. An overview of BPSD: Types of behavioural problems encountered, aetiology of BPSD, approach to treatment of BPSD focusing on person centered care (PCC) and treatment options. For healthcare workers, particularly the ones not trained in geriatric and gerontology, BPSD is challenging and stressful. The majority of caregivers will end up restraining- either physically or chemically, the patients for their safety. Restraining the elderly comes with complications like physical deconditioning, DVT, UTI, urinary retention, constipation, pneumonia, pressure sore, etc. The aim of this presentation is to introduce to the audience the causes of challenging behaviors and how to manage the agitated patients non-pharmacologically, with restraints as a later alternative. The presentation will include 2-3 cases for discussion.

Biography:

Pieter Hasenaar owns a media company and his brother Harm is a architect. Since their mother has Alzheimer's disease, they want from their profession to make a positive and innovative contribution to improving the quality of life for all involved. Together they work on this social project. See for more info: www.dementia-app. com. The brothers are assisted with their project for advice and supported by several organizations in the Netherlands, including case and home care managers of mental health care, health insurance company CZ, and Alzheimer’s Netherlands. There also is a Scientific Advisory Board, which has formed by six Dutch universities and their scientists.

Abstract:

Biography:

Abstract:

Vascular dementia has been reported as the most common form of dementia in South Asian communities living in the UK due to higher incidences of hypertension and diabetes. Research on dementia care in these communities has highlighted the need for the need for cultural competency training for those working professionally with people with dementia and their families. It has been evidenced that while many health professionals feel that they need more training to both improve their knowledge about dementia and the cultural norms and religious practices of South Asian people with dementia, access to this sort of training is variable. Because of the acute lack of quantitative and qualitative data about the health and social care needs of South Asian communities, and how they are best met, training to improve cultural competency in services is difficult. This paper reports the findings of research with Sikh carers of a family member with vascular dementia living in Wolverhampton in the UK, highlighting evidence that demonstrates the diversity of the Sikh community and challenges assumptions of homogeneity. The evidence base presented highlights the importance for understanding the psycho-social perspectives of living with vascular dementia for migrant communities and the need for health care professionals and service managers to apply a person-centered approach to care. This paper will help participants to consider person centered care as a model for practice for achieving cultural competency with migrant communities living with dementia in their countries of work. 

Biography:

Panteleimon Giannakopoulos obtained his MD degree in the University of Athens in 1989 before completing a full training on Psychiatry and Psychotherapy in London (Maudsley Hospital) as well as Post-doctoral training in Paris (La Pitié-Sâlpetrière Hospital, Federation of Neurology). In 1998, he was appointed as an Associate Professor and Medical Head of the Division of Geriatric Psychiatry of the University Hospitals of Geneva. Later on (2004) he obtained the position of Full Professor of Psychiatry in the University of Geneva. From 2003 to 2011, he also assumed a parallel position of Full Professor of Old Age Psychiatry in the University of Lausanne in order to promote the academic careers of junior staff locally. He has been the Chairman of the Department of Mental Health and Psychiatry in Geneva for ten years (2005-2015) and Vice Dean of the Faculty of Medicine in the University of Geneva In-charge of postgraduate and continuous education (2003-2011). From December 1^st 2015, he is the Medical Head of the Forensic Psychiatry Development in Geneva County. 

Abstract:

The presence of cerebral microbleeds has been associated with dementia and cognitive decline, although studies report conflicting results. Our aim was to determine the potential role of the presence and location of cerebral microbleeds in early stages of cognitive decline. Baseline 3T MR imaging examinations including SWI sequences of 328 cognitively intact community-dwelling controls and 72 subjects with mild cognitive impairment were analyzed with respect to the presence and distribution of cerebral microbleeds. A neuropsychological follow-up of controls was performed at 18 months post inclusion and identified cases with subtle cognitive deficits were referred to as controls with a deteriorating condition. Group differences in radiologic parameters were studied by using nonparametric tests, one-way analysis of variance, and Spearman correlation coefficients. Cerebral microbleed prevalence was similar in subjects with mild cognitive impairment and controls with stable and cognitively deteriorating conditions (25%-31.9%). In all diagnostic groups, lobar cerebral microbleeds were more common. They occurred in 20.1% of all cases compared with 6.5% of cases with deep cerebral microbleeds. None of the investigated variables (age, sex, microbleed number, location and depth, baseline Mini-Mental State Examination score, and the Fazekas score) were significantly associated with cognitive deterioration with the exception of education of >12 years showing a slight but significant protective effect (OR, 0.44; 95% CI, 0.22-0.92; P=0.028). The Mini-Mental State Examination and the Buschke total score were correlated with neither the total number nor lobar-versus-deep location of cerebral microbleeds. Cerebral microbleed presence, location, and severity are not related to the early stages of cognitive decline in advanced age.

Biography:

Eva Kudova has been working at the Institute of Organic Chemistry and Biochemistry in Prague, Czech Academy of Sciences (IOCB) since 2002. She completed her PhD in 2009 from Charles University in Prague. Then, she spent 2 years in the lab of Douglas F. Covey, Washington University School of Medicine in St. Louis, Missouri, USA. Since 2011, she works at the IOCB as the project PI at Targeted Research Group of Steroidal Inhibitors. Her main focus of interest is steroidal chemistry, she has been working in this field for more than 10 years. Her major avenue of investigation is design and synthesis of new neuroactive steroidal compounds and structure-activity relationship studies affording NMDARs ligands. Also, she and her colleagues have proposed screening pipeline that should serve as a screening platform for neuroactive steroids targeting CNS diseases and showing neurosteroids´ drug-likeness. 

Abstract:

Neurosteroids are compounds synthesized in the nervous tissue from cholesterol, or steroidal precursors from peripheral sources. It is believed that neurosteroids execute their effects by modulating the activity of different membrane receptors, including the glutamatergic ionotropic receptors, e.g. N-methyl-D-aspartate receptors (NMDARs). The NMDARs play an important role in development, synaptic plasticity, learning, and memory, however, abnormal activation of NMDA receptors have been shown to mediate neuronal degeneration/cell death. To find novel potentially beneficial drugs to treat neurological damage or neurodegeneration is one of the most investigated areas in contemporary pharmacology and neuroscience. Therefore, we have designed and synthesized a library of SMART Steroids – Steroidal Molecules As Rapid-acting Therapeutics. SMART steroids are neuroactive molecules, targeting primarily NMDARs, show neuroprotective properties, and minimal side effects in animal models. Our screening pipeline currently covers physicochemical and biological properties like: (i) solubility (DLS); (ii) lipophilicity (logP, logD, ΔG_solv); (iii) patch-clamp recordings from HEK293 cells assessing NMDAR inhibition rates and IC₅₀ values; (iv) Caco-2 assay, (v) treatment of glutamate and NMDA-induced neurotoxicity (survival rate, caspase-3, intracellular calcium levels, ROS); (vi) in vitro growth of postnatal neurons after neurosteroid administration, (vii) models of animal behavior (open field, elevated plus maze, forced swim test, etc.); (viii) PTZ-induced seizures; (ix) paclitaxel-induced peripheral neuropathy; (x) pharmacokinetic properties. Our results indicate that these compounds do afford neuroprotective effect and as such, SMART steroids may be beneficial in treatment of several neurological diseases like epilepsy, neuropathic pain, AD, PD and others. Broad patent portfolio has been developed protecting compounds, production and its use for treatment in neurology etc. (EP 2313424, US 2012071453, EP 2675821, WO2016029888 A1). Supported by grant TE01020028 Center for Development of Original Drugs from the Technology Agency of the Czech Republic and RVO 61388963.

Biography:

Abstract:

Biography:

Abstract:

Biography:

Abstract:

Biography:

Paula Kielbik is currently PhD student at the Warsaw University of Life Sciences at Faculty of Veterinary Medicine. She completed both her Bachelor and Master of Science degrees under supervision of dr Michal Godlewski in Nanotechnology Laboratory in collaboration wit Polish Intitute of Physics. In her scientific work she focused mainly on biodistribution of biodegradable nanoparticles in the living organism. The main aspect of her work was transfer of nanoparticles through the organism barriers (i.e. intestinal barrier, blood-brain barrier, blood-testis barrier) by ZnO-derieved NPs in adult organism. Working as a member of a team in Nanotechnology Laboratory Paula was involved in the development and assessment of compherehesive methodology for the evaluation of gastrointestinal absorption, circulation and elimination from the organism of biodegradable nanoparticles. 

Abstract:

Zinc oxide nanaoparticles (ZnO NPs) became promising material for numerous applications, includind biomedicine. Avaible reports assessing their biodistribution present contradictory conclusions. Furthermore transfer of NPs through the blood-brain barrier has not been reported extensively. In our study we orally administrated fluorescent¹ ZnO NPs doped with Europim (ZnO:Eu) to mice (n=35). After 3h, 24h, 7d, 14d or 1m mice were sacrificed and internal organs were collected for the assessment of biodistribution and localization of NPs in the organism. For the analyses we proposed a novel comprehensive and innovative approach. Along with the measurement of Zn concentration in organs with spectroscopy method (AAS), we performed quantitative and qualitative cytometric evaluation of collected samples. The distribution patterns of ZnO:Eu NPs within tissues were statistically assessed with scanning cytometry, while the extent of biodegradation was semiquantitatively elucidated by confocal microscopy. Results revealed very rapid and efficient uptake and distribution of ZnO:Eu NPs to key organs and tissues, also crossing physiological barriers. Spleen, as well as fat tissue were responsible for accumulation of NPs, and liver with kidney were designated for their elimination². An interesting pattern of biodistribution of NPs in the brain was also observed. Following 3h after IG administration, we observed crossing of the blood-brain barrier by ZnO:Eu NPs and their uniform distribution in the brain. Similar observations were reported earlier for non-biodegradable ZrO₂:Pr NPs³ and Y₂O₃:Eu NPs⁴. The peek of NPs transfer to the brain seems to take place 24h post IG with majority of NPs allocated in the areas of dense neuronal networks, limbic system and cerebellum. During following days we observed a drop of NPs-related fluorescence, however the association with limbic system and dense neuronal networks remained. We speculate, that elimination of the NPs from the brain might consequential of biodegradation of NPs and their efficient elimination via neuronal transport⁵.

Acknowledgments:

NCN: DEC-2012/05/E/NZ4/02994

NCN: 20/0139/N/ST3/04189