6^th International Conference on Vascular Dementia Feb 27-Mar 01, 2017 Amsterdam, Netherlands

Biography:

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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.

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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.

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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.

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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.

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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.

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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.

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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. 

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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. 

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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.

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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. 

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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.

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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. 

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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

Biography:

Solveig Niklass has her expertise in basic research in the field of cerebral small vessel disease (CSVD) as a cause of acute strokes. She established the 2-photon-microscopy in spontaneously hypertensive stroke prone rats as a tool for intravital imaging of the cerebral vasculature. New dyes for in vivo imaging allow for the simultaneous detection of CSVD and cerebral amyloid pathology, defining the focus of her actual research. 

Abstract:

Statement of the Problem: In human autopsy studies of the non-demented elderly and Alzheimer’s disease non-amyloid cerebral small vessel pathology (CSVD) and cerebral amyloid angiopathy (CAA) are found in the same brain. We here hypothesize a causal link between the two CSVD entities that goes beyond just a simple co-occurrence. We therefore investigated if spontaneously hypertensive stroke-prone rats (SHRSP), a valid non-transgenic animal model of human non-amyloid CSVD, develop CAA as a function of different non-amyloid CSVD stages.

Methodology: Two-photon-microscopy was performed in 21 SHSRP to assess stages of CSVD in vivo. Therefore, the fluorescent dye Dextran was used to label the cerebral vasculature, and cerebral blood flow measures (CBF) were additionally conducted. Furthermore, in 13 out of those 21 SHRSP Methoxy-X04 (Congo red derivate) was used for the intravital CAA detection.

Findings: Non-amyloid CSVD progression occurs in a temporal manner, comprising the following stages: stage 0 – no CSVD pathology, stage 1A – small vessel wall damage, stage 1B – CBF reduction, stage 2 – non-occlusive/ incomplete thrombus formation and stage 3 – occlusive/ complete thrombus formation. Six out of 13 SHRSP (46%) that underwent Methoxy-X04 imaging displayed intravital β-amyloid positivity of the cerebral small vessel walls, i.e. perivascular amyloid deposits and brightly fluorescent arteriolar/small artery wall adherent plane- or circular-shaped amyloid accumulations indicative of CAA. In nearly all Methoxy positive SHRSP amyloid deposits were detected surround thrombotic arterioles characterized by (in)complete small vessel occlusions (CSVD stage 2/3).

Conclusion & Significance: Advanced non-amyloid CSVD stages display a condition prone to vascular β-amyloid accumulations, in terms of CAA. Further investigations have to shed light on the pathophysiological interactions between the two small vessel disease entities, especially whether a failure of perivascular Aβ-drainage or disturbances of endothelial Aβ-transport across the blood brain barrier drives the vascular amyloid pathology found in the SHRSP. 

Biography:

Fan Fan is an Assistant Professor at University of Mississippi Medical Center, USA. Her research focuses on the genetic basis of the impaired myogenic response and auto-regulation of cerebral and renal blood flow and end organ damage in aging, hypertension and diabetes. She has published more than 30 papers. She currently serves as a Peer Reviewer for the American Heart and Alzheimer’s Associations, and is an Editorial Board Member and reviewer for several journals. Her work is funded by the National Institutes of Health (NIH) and the American Heart Association (AHA) to study roles of Add3 (NIH/NIA, NIH/NIDDK), CYP4A1 and 20-HETE (NIH/NIGMS, AHA) on aging and hypertension-related renal and cerebral vascular and dementia.

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Alzheimer's disease (AD) and diabetes (DM) are two of the most common diseases of aging. More than five million Americans have AD, and 29 million Americans have DM. The cumulative incidence of AD is 12.5% and DM is 26.9% among people 65 and older in the US. Evidence suggests that DM is linked with the development of AD, and these diseases are associated with cerebral vascular dysfunction. However, the mechanisms involved have not been fully elucidated. The present studies examine whether the myogenic response of middle cerebral artery (MCA) and auto-regulation of cerebral blood flow (CBF) are impaired in the T2DN rat, a type 2 diabetic (T2DM) strain, and whether these impairments contribute to the development of dementia and AD. Our data indicate that the myogenic response of MCA and auto-regulation of CBF are impaired in T2DN rats with aging. This cerebral vascular dysfunction is in association with blood-brain barrier (BBB) leakage, neurodegeneration and learning and memory dysfunction. Our results also demonstrate that the neurodegeneration in elderly T2DN rats is associated with elevated expression of beta-amyloid (Aβ) and Tau in the brain, suggesting these diabetic rats expresses the characteristic biomarkers of AD. The expression of GFAP and IL-1β is elevated in aged T2DN rats indicating that glial activation and inflammation may link aging, diabetes and cognitive deficits in this model. In summary, our studies suggest that the impaired auto-regulation of CBF plays an important role for the development of cognitive dysfunction and AD, and present information critical to the development of new treatments to prevent elder and DM- related dementia including AD.

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Dr. Ramel Carlos is a practicing neurologist in the Island of Guam for the past 15 years. He completed his residency and fellowship training in Pediatrics, Child Neurology, Epilepsy, and Clinical Neurophysiology at Wake Forest University Baptist Medical Center I n Winston Salem, N.C. He is a diplomate of American Board of Psychiatry and Neurology. He has presented his various clinical researches internationally regarding neurodegenerative diseases including Dementia and Parkinson disease and its association with various vascular diseases. His research on “Silent Strokes and Vascular Diseases in Cognitive Impairment in the island of Guam was awarded the Best Poster Research Presentation in London last March 2016 during the World Congress of Neurology and Therapeutics. He has published 3 books, entitled Essentials of Stroke and Heart Disease, Basic Brain Boosters, and 101 Inspirational Quotes on Health. He obtained his medical.                                                            

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Emerging evidence suggested a link between Obstructive Sleep Apnea (OSA) and cognitive decline, including dementia. The severity of cognitive impairment has been reported to be directly correlated with the degree of OSA. Neurodegenerative changes and vascular diseases are significant comorbidities on these patients.  We report the occurrence of OSA in patients with dementia in the Island of Guam and to correlate the severity of OSA with the results of the neuropsychological testing and neuroimaging studies. We also report the prevalence of comorbid vascular diseases in these patients. A retrospective analysis of medical records of patients evaluated in The Neurology Clinic with the diagnosis of OSA and dementia from August 2006 to June 2016 was conducted. There were 359 patients with dementia and 17% have been diagnosed with OSA.  Among patients with OSA, 45% have moderate to severe OSA with moderate degree of cerebral atrophy on the neuroimaging studies and 17% have mild OSA with mild degree of cerebral atrophy. Seventeen percent of patients with moderate to severe OSA have moderate impairment on global cognitive scores and 17% with mild OSA have mild impairment on global cognitive scores. Twenty five percent of patients with moderate to severe OSA have stroke and 17% have Leukoaraiosis in the neuroimaging studies. The prevalence of vascular diseases on patients with moderate to severe dementia showed that  75%, 58%, 66% and 33% of patients have hypertension, diabetes mellitus, hyperlipidemia and heart diseases, respectively, Wherein patients with mild dementia,  hypertension, diabetes mellitus, hyperlipidemia and heart diseases were identified on 70%, 54%, 60% and 30% of patients, respectively. Conclusion: OSA is a common sleep disturbance in patients with dementia. The severity of OSA correlates closely with the degree of cerebral atrophy and global cognitive scores. Various comorbid vascular diseases are frequently encountered in patients with OSA and dementia. 

Biography:

Prof. Boon Chuan LOW is a Principal Investigator at the Mechanobiology Institute and Department of Biological Sciences, National University of Singapore. His group focuses on defining cellular and molecular mechanisms underlying neuronal differentiation and cancer metastasis. His discovery on the BCH domain as a versatile protein scaffold has led to our better understanding of the intricate spatiotemporal    regulation    of    GTPases,    kinases    and metabolic signaling in cell morphogenesis, cell motility, cell growth and differentiation. His work also extends to BCH and other scaffold proteins that can integrate both biochemical and mechanical signals in cell-cell and cell- matrix interaction, leading to tissue organization and organogenesis.

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The neurotransmitter acetylcholine (ACh) is essential for neuron development, memory, learning and motor movement. It is synthesized from choline and acetyl-CoA by choline acetyltransferase (ChAT). ATP citrate lyase (ACL) is a key metabolic enzyme that produces the acetyl-CoA for this process. However, the precise spatial disposition of this cholinergic machinery for both morphogenesis and neurotransmission remain largely unknown.

Mutations in the ATCAY/Atcay gene, which encodes a BCH domain- containing BNIP-H (also known as Caytaxin), lead to ataxia and mental retardation in humans (Cayman ataxia), as well as ataxia and dystonia in several rodent models. Recently, we used molecular genetics, biochemical and imaging methods and revealed that BNIP-H recruits the cholinergic machinery to neurite terminal to regulate cholinergic signaling (Developmental Cell, 2015). BNIP-H links kinesin-1 (KLC1) motor protein to ACL and transports ACL towards neurite terminal. There, the BNIP-H/ACL complex synergistically recruits ChAT, leading to enhanced secretion of ACh. ACh then activates MAPK/ERK via muscarinic receptors to promote neuritogenesis. In mice deficient in BNIP-H, ACL fails to interact with KLC1, and formation of the ACL/ChAT complex is prevented. Significantly, Bnip-h knockdown in zebrafish causes axon defect of motor neuron through impaired cholinergic pathway, leading to motor disorder. Here, we further show that BNIP-H specifically engages Rab11 GTPases and a component of the actin-based exocyst complex to regulate its dynamic disposition and neurologic function.

In conclusion, BNIP-H promotes cholinergic signaling by trafficking ACL to neurite end, where ChAT is subsequently recruited to regulate the local production of ACh. Our results provide the first molecular evidence that precise spatial regulation of the cholinergic machinery is crucial in neuronal differentiation and neurotransmission, the significance of which will be further discussed.

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Testicular torsion/detorsion (T/D) can  induce depression in pre- and post-pubertal patients. This study was conducted to investigate the psychological impact of testicular torsion and mechanism underlying its depressive-like behaviour, as well as antidepressant-like activity of minocycline and possible involvement of nitric oxide (NO)/cyclic GMP pathway in this paradigm in male rats undergoing testicular T/D. Unilateral T/D was performed in 36 male adult Wistar rats, and different doses of minocycline were injected alone or combined with Nx-nitro-L-arginine methyl ester (L-NAME), non-specific NO synthase (NOS)inhibitor; aminoguanidine (AG), specific inducible NOS inhibitor;L-arginine, an NO precursor; and selective PDE5I, sildenafil. After assessment of locomotor activity in open-field test, immobility times were recorded in the forced swimming test (FST). Moreover, 30 days after testicular T/D, testicular venous testosterone and serum nitrite concentrations were measured. A correlation was observed between either a decrease in plasma testosterone or an increase in serum nitrite concentrations with prolongation in immobility time in the testicular T/D-operated rats FST. Minocycline (160 mg/kg) exerted  the highest significant antidepressant-like effect in the operated rats in the FST (p<0.001). Furthermore,   combination   of  subeffective doses of minocycline (80 mg/kg) and either L-NAME (10 mg/kg) or AG (50 mg/kg) demonstrated a significant robust antidepressant-like activity in T/D group (p<0.01). Consequently, NO/cGMP pathway was involved in testicular T/D-induced depressive-like behavior and antidepressant- like activity of minocycline in the animal model. Moreover, a contribution was observed between either decreased testosterone or elevated serum nitrite levels and depressive-like behaviour following testicular T/D.

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Evidence show that gamma-aminobutyric acid (GABA) receptors are involved in depression, so the aim of this study was to investigate the effect of nitrazepam as agonist of GABAA receptors on depression and curiosity in male mice and the role of potassium channel in antidepressant-like response. For this purpose, we studied the antidepressant-like properties of fluoxetine, nitrazepam, glibenclamide, and cromakalim by both forced swimming test (FST) and tail suspension test (TST). Animals were injected by various doses of nitrazepam (0.05, 0.1, and 0.5 mg/kg). Nitrazepam at dose of 0.5 mg/kg significantly  decreased the immobility time compared to control group in both FST and TST. Fluoxetine also showed such a response. Co-administration of nitrazepam (0.05 mg/kg) with glibenclamide in TST (1 mg/kg) and in FST (0.3, 1 mg/kg) also showed antidepressant- like response. Beside, cromakalim (0.1 mg/kg) could reverse the antidepressant-like effect of nitrazepam (0.5 mg/kg) in both  FST    and    TST,    while    cromakalim   and glibenclamide alone could not change the immobility time compared to control group (P40.05). The hole-board test revealed that nitrazepam at doses of 0.5 and 0.1  mg/kg could increase the activity of the animal’s head-dipping and boost the curiosity and  exploration  behavior  of mice.

The results of this study revealed that nitrazepam may possess antidepressant-like properties and this effect is dependent to potassium channels in   both FST and TST.

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Cirrhosis is associated with cardiac chronotropic and inotropic dysfunction which is known as cirrhotic cardiomyopathy. Cardiac responsiveness to adrenergic stimulation is impaired in cirrhosis. Moreover there is vagal nerve dysfunction which is related to neuromodulatory dysfunction of the angiotensin II in the cirrhosis. This study was aimed to explore the hypothesis that administration of Losartan-angiotensin II receptor antagonist- increases cadiac chronotropic response to isoproterenol in cirrhotic rats; and if so, whether this is associated with altered cardiac TGF-β receptor expression. Cirrhosis was induced by surgical ligation of the bile duct (BDL) in male Wister rats. Half of the BDL-group and control group were treated with losartan for four weeks. Four weeks after bile duct ligation or sham surgery the atria were isolated and spontaneously beating rate and chronotropic responsiveness to β-adrenergic stimulation was assessed using standard organ bath. Pathological assessment was done on the atria. Moreover the expression of TGF-β was assessed the atria using quantitative RT-PCR. Bile duct ligation could induce a significant hypo-responsiveness to adrenergic stimulation. In cirrhotic rats, the chronotropic responses increased after chronic treatment with losartan but it was not significant. Pathological study showed that losartan decreases fibrosis in atria in losartan treated cirrhotic group. TGF-β expression is markedly increased in cirrhotic rats which is significantly decreased in atria following administration  of  losartan.  These  results  might be considered as angiotensin II role in cirrhotic cardiomyopathy but further studies are required to elaborate the mechanism as well as possible advantage of losartan. We conclude that cirrhosis in rats is associated with altered expression of TGF-β in atrium which losartan can ameliorate it.

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Dr. Stefanos Ioannidis is currently working at Royal Free Hospital in United Kingdom. Dr. Ioannidis has published several original research papers in reputed and peer reviewed journals and also participated into several scientific meetings. His research mainly focuses on the neurodegenerative disorders and dementia.

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Introduction: Posterior cortical atrophy (PCA) is a neurodegenerative disorder of progressive dementia, preceded by visuospatial, visuoperceptual deficits, and visual agnosia. It has an age of onset at 50 to 65 years. Here, we describe a case of PCA presenting at an older age with predominant complaint of memory loss.

Case Presentation: 80-year-old, right-handed man with education level at 14 years of age, presented to the memory clinic with 9-month history of episodic memory loss. This was reflected in his Addenbrooke’s cognitive examination III (52/100). He also reported visual impairment for 1 year and inability to judge distances when climbing stairs despite lack of finding in his ophthalmology assessment. He retained his ability to read albeit relying on newspapers with contextual cues such as colorful illustrations. Clinical examination and neuropsychometric evaluation showed optic ataxia, simultanagnosia, visuospatial and visuoperceptual impairment (Rey Complex figure) as well as impaired praxis (Rivermead Behavioural Memory Test). Computed tomography (CT) showed posterior parietal lobe atrophy with preserved hippocampus (Fig A). Positron emission tomography (PET) showed reduction of uptake in the posterior cortex (Fig B), in keeping with a diagnosis of PCA.

He was treated with donepezil and referred to PCA support groups.

Discussion: In elderly patients presenting with impaired memory, the diagnosis of PCA needs to be considered. Patients often develop a compensatory strategy with the visual deficit while disabling cognitive difficulties take hold, which mask the presence of PCA. Moreover, the emphasis on age as part of the diagnostic picture may inadvertently exclude older patients given that younger, working age patients are more likely to be acutely aware of visual problems and thus present to physicians. PCA may therefore be more common in older adults than previously suspected. Correctly identifying the disease process is crucial for patient management including provision of help in perceptual activities.

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