International Conference on Parkinson’s Disease & Movement Disorders August 11-13, 2015 Frankfurt, Germany

Chair

Kjell Fuxe

Karolinska Institutet, Sweden

Session Introduction

Micheal Ugrumov

Institute of Developmental Biology RAS, Russia

Title: Neuroplasticity in the nigrostriatal system of MPTP-treated mice at presymptomatic and early symptomatic stages of Parkinsonism

Time : 11:40-12:10

Biography:

Michael Ugrumov, academician of Russian Academy of Sciences has completed his MD at Institute of Evolutionary Physiology & Biochemistry (Leningrad), PhD at Institute of Developmental Biology, Professorship at University Medical School (Moscow). Head of Laboratory of Neural and Neuroendocrine Regulations at Institute of Developmental Biology RAS, Vice-President of Russian Physiological Society. Member of European Academy of Science and Arts, Serbian Academy of Science and Arts, French National Academy of Pharmacy. He has published more than 200 papers in peer reviewed journals and served as an editorial board member of 8 International and Russian journals.

Abstract:

Parkinson’s disease (PD) is characterized by a long development at preclinical (asymptomatic) stage and the first appearance of motor dysfunctions at a loss of most dopaminergic (DA-ergic) neurons, nigral cell bodies and striatal axons, and a depletion of 60-70% DA in the striatum. The goal of this study was to search mechanisms of neuroplasticity serving to prevent motor dysfunctions at presymptomatic stage and the triggers of a transition to symptomatic stage evaluating DA synthesis (tyrosine hydroxylase (TH) mRNA, protein, activity), release (microdialysis in vivo, slices), uptake (slices), degradation (MAO mRNA, activity) at original models. At presymptomatic stage motor dysfunctions were prevented due to plasticity of survived DA-ergic neurons that was manifested by enhanced TH activity, increased spontaneous and stimulated release of DA, and decreased MAO B activity. Noteworthy, striatal DA was synthesized not only in DA-ergic axons but also in non-dopaminergic neurons containing individual enzymes, TH or aromatic L-amino acid decarboxylase, in cooperation. At symptomatic stage, despite maintaining of DA synthesis in DA-ergic neurons at the control level and an increase of DA synthesis in monoenzymatic neurons, intercellular level of DA dropped up followed by an appearance of motor disorders. Major triggers of motor dysfunctions appeared to be a decrease of spontaneous and stimulated release of striatal DA and an increase of MAO A activity. PD models of preclinical and early clinical stages, specified in this study are suitable for development of preventive pharmacotherapy serving to improve compensatory processes and inhibit triggers of motor dysfunctions.

Geeta Shroff

Nutech Mediworld, India

Title: Use of human embryonic stem cells in the treatment of Parkinson’s disease

Time : 12:10-12:40

Biography:

Geeta Shroff has developed the technology to isolate Human Embryonic Stem Cells (hESC), culture them, prepare them for clinical application and store them in readyto- use form with a shelf life of six months. Since 2002, more than 1300 patients suffering from various conditions like spinal cord injuries, diabetes, multiple sclerosis, Parkinson’s disease, cardiac conditions, cerebral palsy have been treated by her. She is a Graduate in Medicine from the University of Delhi and did her Postgraduation in Gynaecology & Obstetrics. She further specialized in treating Infertility and is a Trained Embryologist and a qualified IVF practitioner. After gaining 8 years of valuable clinical experience at Safdarjung Hospital & Batra Hospital, she set up her own IVF practice in 1996. She has begun research on human embryonic stem cells in 1999 and pioneered in human embryonic stem cell therapy. She has presented her work at various national and international forums.

Abstract:

Parkinson’s disease (PD) is a disorder of central nervous system characterized by rigidity, tremor and hypokinesia. Pharmacological and non-pharmacological methods do not improve the quality of life permanently. We used Human Embryonic Stem Cells (hESCs) to treat a 65-year old male patient with PD. Patient had back and neck stiffness, resting tremors, bradykinesia, muscle rigidity, unclear speech and imbalanced walking. SPECT scan showed moderate hypoperfusion in bilateral parieto-temporal regions and moderate-to-severe hypoperfusion in bilateral basal ganglia and bilateral cerebellar regions. hESCs were cultured and maintained in a GMP, GLP and GTP compliant laboratory using patented technology. Safety and efficacy of these hESCs is established. Treatment consisted of four phases (T1, T2, T3 and T4) with gap phases. hESCs were given through i.v. (1 ml twice a week), i.m. (0.25 ml twice daily), supplemental routes (1-5 ml every week) and via nasal sprays (3.5 ml twice a week). After 12 months of therapy, patient showed remarkable improvement in health with reduction in tremors, muscle rigidity, bradykinesia and stiffness in neck, shoulder and low back pain. Patient experienced reduction in apathy in left hand and legs and was able to balance himself while walking. He was able to speak louder. SPECT scan and MRI showed normal hypoperfusion in the cerebral region of the patient. No adverse event and teratoma formation was observed. Patient is being followed up regularly and is taking no medications. He has mild tremor in right hand. hESC therapy benefitted our patient with PD but further studies are needed to gather more evidence.

Break: Lunch Break 12:40-13:30 @ Restaurant

Audun Myskja

Norges Parkinson for bund, Norway

Title: Evaluation of a rhythmic exercise program for patients with Parkinson’s disease

Time : 13:30-14:00

Biography:

Audun Myskja is a Doctor, Music Therapist, Leader and Founder of ‘Senter for Livshjelp’ (LifeAid Centre for empowerment). His career has encompassed not only allopathic medicine (since 1981) but he has also gained considerable recognition in Norway and other countries for his work in a number of complementary therapies. He worked in general practice and internal medicine during 1982-1998; was educated in complementary therapies and integrated medicine from 1974; and practiced with, healing, herbs and flower essences from 1976. He is an Author for 20 books and 100+ articles on integrated medicine, medical music therapy, self-development, ecology, spirituality, meditation, exercise, health building. He is a Collaborator with Norwegian Parkinson`s disease Association from 2002.

Abstract:

Objective: To evaluate a structured training program using a series of rhythmic exercises for a group of patients with Parkinson’s Disease (PD). Background: There is increasing interest in the potential benefit of systematic exercise in the management of PD. However, there is still insufficient knowledge about what type of exercise may be most beneficial for which symptoms and how exercise programs may be best applied to aid PD patients. Methods: PD patients (n=20) were recruited in a Norwegian region with patients on waiting list as controls. The group followed a structured program with rhythmic exercises once a week led by physiotherapist. The mean age was 62.4 (SD 7.3) years and the mean disease duration was 8 (SD 5.2) years. Participants were evaluated by UPDRS, Hoehn & Yahr, Senior Fitness, Up and Go before project start at 6, 12 and 18 months. Quality of life issues were evaluated by interactive qualitative interviews, Montgomery- Aasberg depression rating scale and Herth Hope Index before project start at 6, 12 and 18 months. Results: Functional tests showed stability in the exercise group compared to control group. Quality of life measures showed low values for depression compared to control group and emphasized the value of group training and the importance of collaboration with participants responses. Interview data suggest that a higher rate of follow-up on home training would further improve results. Conclusions: Our follow-up data from the 4 year period 2011-15 suggest benefit of a rhythmic exercise program developed in collaboration with participants, effects becoming more marked over time. Further research to specify benefits of structured exercise is recommended.

Sanjay Jaiswal

Jaiswal Hospital and Neuro Institute, India

Title: Dyskinesia associated with old and new therapies in Parkinson’s disease

Time : 14:00-14:30

Biography:

Sanjay Jaiswal has completed his MD from RNT Medical College, Udaipur, India and DM Neurology from Institute of Medical Sciences BHU, Varanasi, India. He is a Consultant Neurologist at Jaiswal Hospital and Neuro Institute, Kota, Rajasthan, India. He has published several papers in reputed journals and has been serving as a Faculty in most of the neurology conferences. He has got an extensive experience of organizing and conducting conferences in the field of neurology and has been awarded by State Government for the contribution to social welfare.

Abstract:

Parkinson’s disease is a neurodegenerative disorder that affects approximately 1% of people over the age of 60 years. Levodopa is standard, and often initial, therapy for patients with this condition. However, with continued treatment and as the disease progresses, up to 80% of patients experience ‘wearing-off’ symptoms, dyskinesia and other motor complications. Younger age of Parkinson’s disease onset, disease severity, and high levodopa doses increase the risk of development of levodopa‐induced dyskinesia (LID). Recent studies indicate the importance of pulsatile stimulation of striatal postsynaptic receptors in pathogenesis of LID. The non‐human primates with MPTP‐induced Parkinsonism serve as a useful model to study dyskinesia. Once established, LID is difficult to treat and, therefore, efforts should be made to prevent it. The therapeutic and preventative strategies for LID include using a lower dosage of levodopa, employing dopamine agonists as initial therapy in Parkinson’s disease such as amantadine, use of atypical neuroleptics and neurosurgery. In recent studies, among 124 patients with Parkinson’s disease, 87 (70%) had received a levodopa preparation. Among these 87 patients, 28% were experiencing treatment-induced dyskinesias and 40% showed response fluctuations. The newer, non-ergoline dopamine agonists such as pramipexole and ropinirole have undergone extensive studies to evaluate their efficacy as monotherapy in early Parkinson’s disease. Amantadine is a non-competitive NMDA receptor antagonist shown to lower dyskinesia scores and improve motor complications in patients with Parkinson’s disease when given adjunctively with levodopa. These newer agonists are ideal initial symptomatic medications, primarily because they delay the onset of levodopa-induced motor fluctuations. So, it can be concluded that there is less chances of developing dyskinesia when patient is on newer anti parkinsonian drugs as compared to older agents.

Chair

Kjell Fuxe

Karolinska Institutet, Sweden

Session Introduction

Jie Bai

Kunming University of Science and Technology, China

Title: Thioredoxin-1 suppresses MPP+/MPTP neurotoxicity through enhancing autophagy

Time : 10:00-10:30

Biography:

Jie Bai, now vice dean at Kunming University of Science and Technology, China. He established the ground-breaking neuroscience research programme on Parkinson’s disease (PD) with his novel human stem-cell-based cellular model of PD, aiming to find mechanism(s) of cell damage that leads cell towards death and development of the PD.

Abstract:

Autophagy is a lysosomal degradative process used to recycle obsolete cellular constituents and eliminate damaged organelles and misfolded protein. Autophagy is associated with the pathogenesis of Parkinson’s Disease (PD). Thioredoxin-1 (Trx-1) is a redox regulating protein and plays an important role in PD. However, the relationship between autophagy and Trx-1 in PD has not been reported. Cell and mouse models of PD were used to examine the relationship of autophagy and Trx-1. We showed that the expression of microtubule-associated protein light chain 3 (LC3-II), an auto-phagosome membrane marker was induced by 1-methyl-4-phenylpyridinium ion (MPP+)/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in PC12 cells and mice. Rapamycin autophagy inducer decreased toxicity by MPP+ in contrast to chloroquine autophagy inhibitor which increased toxicity by MPP+. These results suggest that autophagy plays a protecting role against MPP+ neurotoxicity. The over-expression of Trx-1 in PC12 cells and mice reversed LC3-II expression by MPP+/MPTP. Importantly, Forkhead box O3A (FOXO3A) expression was decreased by MPP+/MPTP in PC12 cells and Substantia Nigra pars compacta (SNpc) of mice. The decrease of FOXO3A was enhanced by down-regulation of Trx-1 and reversed by Trx-1 over-expression in mice. These results suggest that Trx-1 suppresses MPP+/MPTP neurotoxicity by enhancing FOXO3A/autophagy pathway. Our present study indicates FOXO3A may be a new potential target for treatment of PD.

Dasiel O Borroto-Escuela

Karolinska Institutet, Sweden

Title: On the role of A1-D1 heteroreceptor complexes in the direct pathway in models of Parkinson’s disease

Time : 10:30-11:00

Biography:

Dasiel O Borroto-Escuela has completed his PhD from Polytechnic University of Catalonia, Spain. Since 2009, he has been a Contracted Postdoctoral Researcher at the Department of Neuroscience, Karolinska Institutet. His primary focus is on understanding whether alterations in specific heteroreceptor complexes and if their receptor-receptor interactions are associated with and/or play a role in pathogenetic mechanisms contributing to brain disease development, inter alia Parkinson’s disease, schizophrenia, addiction and depression. He has received a significant number of awards, among which are the UPC Excellence Thesis Award, the FEBSYSF 2013, the ECNP 2014 Fellow Award. He has published over 70 papers in neuroscience in the last five years. His major achievements involve pioneering work on understanding the molecular integration of signals in the brain via receptor-receptor interaction in heteroreceptor complexes and its functional effects also, in the implementation of new innovative tools and screening technologies to identify GPCR oligomers.

Abstract:

Among a large number of behavioural studies on adenosine A1-Dopamine D1 receptor interactions, a few examples may be given. Thus, the A1 receptor agonist CPA counteracted the D1 receptor agonist (SKF 38393)-induced grooming behavior and counteracted dyskinetic behavior in rabbits. In line with these results, the A1 receptor antagonist CPT enhanced the motor activating effects of the D1 agonist SKF 38393 in reserpinized mice and in rat models of Parkinson’s disease (unilateral 6-OH-dopamine lesions of the nigrostriatal dopamine pathway). This behavioural result at the network level indicates the existence of antagonistic A1-D1 receptor interactions. The molecular basis of the antagonistic A1-D1 receptor interaction likely involves the existence of A1-D1 heteroreceptor complexes in the direct pathway. The A1-D1 heteroreceptor complexes may reflect a direct physical interaction without the involvement of an adapter protein, since specific BRET and FRET signals can be detected between fluorescent-tagged A1 and D1 receptors upon transient co-transfection in cell lines. Furthermore, in situ Proximity Ligation Assay clearly demonstrated that A1 and D1 receptors exist as heteroreceptor complexes in rat brain. Antagonistic A1-D1 interactions also exist at the level of the second messengers. These results suggest a role of A1 receptor agonists and antagonists in the treatment of Parkinson’s disease with dysfunction of D1 receptor signaling via their actions on the A1-D1 heteroreceptor complexes located in the direct pathway. A1 agonists may, for example, reduce levodopa induced dyskinesias. It will be of substantial interest to know how the A1-D1 receptor interaction may regulate trophic mechanisms such as neurotrophic factors and neuronal differentiation.

Break: Coffee Break 11:00-11:30 @ Foyer

Kjell Fuxe

Karolinska Institutet, Sweden

Title: The impact of DA heteroreceptor complexes and their receptor-receptor interactions in Parkinson’s disease and its treatment

Time : 11:30-12:00

Biography:

Kjell Fuxe is a Professor of Histology at Karolinska Institutet since 1979. He was the Member of Nobel Assembly from 1986-2005. He achieved his Honorary Doctorates at the Universities of Barcelona, Ferrara, Malaga, at Universite Claude Bernard, Lyon, at Marquis Guiseppe Scicluna International University Foundation and at the Albert Einstein International Academy Foundation. He has received a significant number of awards and published over 1500 papers in neuroscience. 1209 of them are found in Pubmed. His major achievements involve pioneering work on central monoamine neurons, the existence of volume transmission, receptor-receptor interactions in heteroreceptor complexes and in neuro-endocrinology and neuro-psychopharmacology.

Abstract:

Several types of D2R and D1R heteroreceptor complexes were discovered in the indirect and direct pathways of the striatum, respectively. Changes in the function of the DA heteroreceptor complexes may help us understand the molecular mechanisms underlying the motor complications of long-term therapy in Parkinson’s Disease (PD) with levodopa and DA receptor agonists. In the indirect pathway, the potential role of the A2AR-D2R, A2AR-D2R-mGluR5 and D2R-NMDAR heteroreceptor complexes in PD will be covered; and in the direct pathway, the D1R-D3R, A1R-D1R, D1R-NMDAR and putative A1R-D1R-D3R heteroreceptor complexes in PD will be covered. D1R and D2R heteroreceptor complexes in the brain open up a new understanding of the wearing-off of the anti-Parkinson actions of levodopa and DAR agonists and the production of levodopa induced dyskinesias. Today, it seems as if the major advantage of DA receptor agonists is that they can postpone, in early PD, the use of levodopa which gives a higher incidence of dyskinesias in PD patients vs. ropinirole and pramipexol. The motor complications can involve a reorganization of the D1R and D2R heteroreceptor complexes and a dis-balance of the D1R and D2R homomers versus non- DA receptor homomers in the direct and indirect pathways. Through understanding these mechanisms, new strategies for the treatment of motor function deficits in PD can be offered with reduced motor complications. However, the motor deficits due to degeneration of non-dopaminergic neurons will remain.The relevance of interactions of the receptor protomers in the signaling cascades and the transcriptional regulation will also be discussed including downstream target proteins.

Jose L Lanciego

Center for Applied Medical Research, Spain

Title: New gene therapy approaches for Parkinson’s disease

Time : 12:00-12:30

Biography:

Jose L Lanciego has completed his PhD from the University of Salamanca Medical School and Postdoctoral studies from Amsterdam Vrije Universiteit. He is the Director of the Basal Ganglia Neuroanatomy Lab at the Center for Applied Medical Research (CIMA). He has published more than 80 papers in international scientific journals and he is serving as an Editorial Board Member of Brain Structure and Function as well as Associate Editor of Frontiers in Neuroanatomy. His main research interests include a number of topics dealing with the pathophysiology of Parkinson’s and Alzheimer’s diseases.

Abstract:

The field of Gene Therapy in the CNS has recently witnessed a number of major conceptual changes. Besides the traditional thinking that comprises the use of viral vectors for the delivery of a given therapeutic gene, a number of original approaches have been recently envisaged, focused on using vectors carrying genes to further modify brain circuits of interest. It is expected that these approaches will ultimately induce a therapeutic potential being sustained by induced changes in brain circuits. Here, we will illustrate the rationale behind several experiments that are currently under implementation in the Non- Human Primate (NHP) model of Parkinson’s Disease (PD). Among others, we will focus on the following approaches: (1) In vivo reconstruction of the nigro-striatal pathway, (2) Selective elimination of hyperactive basal ganglia circuits in dyskinetic macaques and (3) Strategies for in vivo reprogramming of striatal neurons. Besides considering the translational potential of these approaches, we hope that these experiments, complementary to each other, will allow us to generate new data supporting a better understanding of the pathophysiology of PD.

Break: Lunch Break 12:30-13:30 @ Restaurant

Session Introduction

Kjell Fuxe

Karolinska Institutet, Sweden

Title: The impact of DA heteroreceptor complexes and their receptor-receptor interactions in Parkinson’s disease and its treatment

Time : 14:30-15:30

Biography:

Kjell Fuxe is a Professor of Histology at Karolinska Institutet since 1979. He was the Member of Nobel Assembly from 1986-2005. He achieved his Honorary Doctorates at the Universities of Barcelona, Ferrara, Malaga, at Universite Claude Bernard, Lyon, at Marquis Guiseppe Scicluna International University Foundation and at the Albert Einstein International Academy Foundation. He has received a significant number of awards and published over 1500 papers in neuroscience. 1209 of them are found in Pubmed. His major achievements involve pioneering work on central monoamine neurons, the existence of volume transmission, receptor-receptor interactions in heteroreceptor complexes and in neuro-endocrinology and neuro-psychopharmacology.

Abstract:

Several types of D2R and D1R heteroreceptor complexes were discovered in the indirect and direct pathways of the striatum, respectively. Changes in the function of the DA heteroreceptor complexes may help us understand the molecular mechanisms underlying the motor complications of long-term therapy in Parkinson’s Disease (PD) with levodopa and DA receptor agonists. In the indirect pathway, the potential role of the A2AR-D2R, A2AR-D2R-mGluR5 and D2R-NMDAR heteroreceptor complexes in PD will be covered; and in the direct pathway, the D1R-D3R, A1R-D1R, D1R-NMDAR and putative A1R-D1R-D3R heteroreceptor complexes in PD will be covered. D1R and D2R heteroreceptor complexes in the brain open up a new understanding of the wearing-off of the anti-Parkinson actions of levodopa and DAR agonists and the production of levodopa induced dyskinesias. Today, it seems as if the major advantage of DA receptor agonists is that they can postpone, in early PD, the use of levodopa which gives a higher incidence of dyskinesias in PD patients vs. ropinirole and pramipexol. The motor complications can involve a reorganization of the D1R and D2R heteroreceptor complexes and a dis-balance of the D1R and D2R homomers versus non- DA receptor homomers in the direct and indirect pathways. Through understanding these mechanisms, new strategies for the treatment of motor function deficits in PD can be offered with reduced motor complications. However, the motor deficits due to degeneration of non-dopaminergic neurons will remain.The relevance of interactions of the receptor protomers in the signaling cascades and the transcriptional regulation will also be discussed including downstream target proteins.

Break: Coffee Break 15:30-16:00 @ Foyer

Session Introduction

Marleen Huijben-Schoenmakers

University of Amsterdam

Title: The effects of increased therapy time on cognition and mood in frail patients with a stroke who rehabilitate on rehabilitation units of nursing homes in the Netherlands: A protocol of a comparative study

Time : 16:00-16:30

Biography:

Marleen Huijben-Schoenmakers has completed her Master of Science (Nursing) at the University of Utrecht. Furthermore, she studied Ethical Care at the Radboud University of Nijmegen and presently, she is a PhD Candidate at the Free University of Amsterdam and she is a Lecturer at the Avans University for Applied Sciences in Breda, Netherlands. Her research topics are focused on stroke rehabilitation. She has developed and implemented the exercise map on stroke units in nursing homes and by this the therapy time increased significantly by 50% to 150 minutes a day. She is now examining if the increased therapy time affects cognition in stroke patients

Abstract:

Background: Recovery after stroke is dependent on how much time can be spent on rehabilitation. Recently, we found that therapy time for older stroke patients on a rehabilitation unit of a nursing home could be increased significantly from 8.6 to at least 13 hours a week. This increase was attained by the implementation of interventions focused on strength, mobility and balance. Nurses carried out these exercises with the patients during their daily activities. The aim of the present study is to investigate if increased therapy time has a positive effect on cognition, mood (depression and anxiety) and ADL in stroke patients. Methods: A comparative single blind controlled study will be applied. Patients suffering from a stroke and staying in one of the rehabilitation units of the nursing homes are eligible for participation. Participants belong to the intervention group if they stay in two nursing homes where four interventions of the Clinical Nursing Rehabilitation Stroke Guidelines were implemented. Participants, who stay in two nursing homes where therapy is given according to the Dutch Stroke Guidelines, are included in the control group. Clinical neuropsychologists will assess patients’ cognitive functioning, level of depression (mood) and anxiety. Nurses will assess a Barthel Index score on a weekly basis (ADL). These variables are measured at baseline after 8 weeks and at the moment when participants are discharged from the nursing home. Discussion: The present study evaluates the effect of increased therapy time on cognition, mood (level of depression and anxiety) and ADL in stroke patients. When positive effects will be found this study can guide policy makers and practitioners on how to implement more therapy time on rehabilitation wards of nursing homes.

Arunasalam Balamanogaran

Gomel State Medical University, Belarus

Title: Hyperkinetic movement disorders, differential diagnosis and treatment

Time : 16:30-17:00

Biography:

Arunasalam Balamanogaran studying at Gomel state Medical University in Belarus. He was interested in medical researches. He had good research experience and knowledge with pharmacology, path physiology, neurology.

Abstract:

Parkinson’s disease, the most common hypokinetic movement disorder, has received much attention from the clinical and scientific community, but there has been a relative paucity of comprehensive reviews of hyperkinetic disorders, even though they are equally or even more disabling. Hyperkinetic movement disorders include tremors, dystonia, chorea, tics, myoclonus, stereotypies, restless legs syndrome, and various other disorders with abnormal involuntary movements. Substantial progress has been made in the understanding of the role of the basal ganglia in the pathophysiology of these hyperkinesia disorders and in motor control, muscle tone, posture, and cognitive processes. Although therapies that target pathogenesis are still lacking, effective management of hyperkinetic movement disorders demands that physicians are knowledgeable about current and novel pharmacological and surgical approaches. In addition to tetrabenazine, a monoamine-depleting drug, new formulations of botulinum toxin are being increasingly used in the treatment of these movement disorders. Finally, success with surgical approaches, particularly deep brain stimulation in patients with Parkinson’s disease who have levodopa-induced dyskinesia’s, has been extended to the treatment of many hyperkinetic movement disorders.

Chair

Ekaterina Rogaeva

University of Toronto, Canada

Session Introduction

George Stoica

Texas A&M University, USA

Title: Movement Disorder and Neurodegeneration in a Rat Model with Myosin 5a Mutation

Time : 11:40-12:10

Biography:

George Stoica, DVM, MSc., PhD is a professor in the department of Veterinary Pathobiology at Texas A&M University, USA. He received his master degree in veterinary pathology from Ohio State University and PhD in experimental pathobiology from Michigan State University. He is with Texas A&M University since 1984 and advanced to full professor in 1996. His area of expertise is in experimental neuropathology and his area of research span from chemical carcinogenesis, viral carcinogenesis, comparative neurooncology and neurodegenerative disorders in animal models. He published over 100 scientific articles in peer review journals and wrote several chapters in various books.

Abstract:

Myosin5a (Myo5a) is an actin-dependent motor protein that is highly expressed in the brain, and involved in vesicular/organelles transport and its absence leads to movement disorders in humans and animal species (Griscelli and Elejalde syndromes in humans), rodents (dilute lethal phenotype in mice, and diluteopisthotonus of Wistar rats), and Arabian horses Lavender Foal Syndrome. A spontaneous autosomal recessive rat model for neurodegeneration caused by a mutation in the Myo5a gene was developed in our laboratory. The pleiotropic effects of this mutation affect the coat color, central nervous and neuroendocrine systems. Preliminary data from our model of Myo5a mutant Berlin-Druckrey (BD-IV) “shaker” rats demonstrated marked alterative changes involving the alpha-synuclein (α-syn) overexpression, decrease dopamine (DA) levels, alteration of DA metabolism, and overexpression of tau protein in specific anatomical areas of brain in shaker rats compared with non-affected siblings. The movement disorder and alterative biochemical changes increased in severity after 15 days postnatal. The mechanisms responsible for neurological phenotypes in the deficient Myo5a affected animals are less understood and deserve further investigation. Possible role of diverse myosins in synaptic transmission or plasticity has not been investigated. Similar neurological degenerative changes are common in human neurodegenerative diseases such as Alzheimer, Parkinson’s, and Lewis Body dementia, which make this animal model ideal for mechanistically investigating human diseases with potential development of novel therapy, which can lead to translational studies. The main challenge for the future will be to investigate the molecular mechanisms of Myo5a neurodegeneration and its interaction with other proteins underlying its functions.

Ekaterina Rogaeva

University of Toronto, Canada

Title: Mutation analysis of CHCHD10 in neurodegenerative diseases, including Parkinson’s disease

Time : 12:10-12:40

Biography:

Dr. Ekaterina Rogaeva obtained her PhD in Biochemistry at Moscow State University (Russia) in 1988. Researcher, Tanz Centre for Research in Neurodegenerative Diseases, she is an associate professor form university of Toronto. She played a central role in the discovery and characterization of the two presenilin genes responsible for the most aggressive early-onset form of Alzheimer’s disease.

Abstract:

A recent study by Bannwarth et al. implicated CHCHD10 as a novel gene for amyotrophic lateral sclerosis/frontotemporal lobar degeneration (ALS/FTLD). Affected family members were presented with a complex phenotype that included symptoms of ALS, FTLD, cerebellar ataxia, Parkinson's disease (PD) and a mitochondrial myopathy associated with multiple mitochondrial DNA deletions. So far, seven missense CHCHD10 mutations have been reported in patients with a broad phenotypic range. Notably, mitochondrial dysfunction has been implicated in several neurodegenerative diseases. Hence, we sequenced CHCHD10 in 204 ALS, 153 PD, 158 FTLD and 141 Alzheimer’s disease (AD) patients, as well as 497 normal controls. We identified two known pathogenic mutations in three ALS patients (p.R15L and p.P80L); as well as two novel substitutions in two FTLD patients (p.P23T and p.A35D). Finally, we detected a p.P34S substitution in PD patient, who has no symptoms of muscle weakness, dementia or ALS. The same p.P34S variant was also detected in two AD cases, but it did not segregate with AD in the available family. The p.P34S variant was previously reported in unrelated FTLD/ALS and ALS patients. However, the p.P34S substitution was found at comparable frequencies in our control samples and public databases, suggesting that this variant is not pathogenic, which is important in the utility of genetic screening in patient care. The frequency of the CHCHD10 mutations in our datasets is 2.6% for familial ALS, 1.2% for sporadic ALS, 1.6% for familial FTLD, and 1% for sporadic FTLD. All mutation carriers are characterized by atypically long duration and slow disease progression. In conclusion, our study supports the causal role of CHCHD10 mutations in both ALS and FTLD, but not in AD or PD. Intriguingly, the mutations in the CHCHD2 gene (structurally similar to CHCHD10) were very recently reported to cause PD in Japanese patients. The mutation analysis of CHCHD2 in Canadian PD dataset is ongoing and will be presented.

Soliman Khatib

MIGAL–Galilee Research Institute, Israel

Title: Analysis of volatile organic compounds in rats with dopaminergic lesion: possible application for early detection of Parkinson’s disease

Time : 12:40-13:10

Biography:

Soliman Khatib, now is a Research Associate in the laboratory of oxidative stress Migal-Galilee Research institute and a Senior lecturer, Department of Biotechnology Tel-Hai academic collage. Doctor's degree (Ph.D.) (direct Ph.D. program), Technion institute, Natural Science, Chemistry1996-2000. BSC, Ben-Gurion University, Natural Science, Chemistry 1993-1995. My research focus on understanding the relationship between oxidative stress and diseases related to oxidative stress, we identify volatile organic compounds (VOCs) as early biomarkers of Parkinson and other neurodegenerative diseases.

Abstract:

Parkinson's disease (PD) is characterized by dopaminergic (DA) neuron depletion. Early detection of PD may help in selecting the appropriate treatment. Biomarkers of PD have been suggested, however none of these is currently in clinical use. The aim of this study was to identify volatile organic compounds (VOCs) as early biomarkers of PD. Our hypothesis was that during PD progression, specific VOCs are generated that are linked to the biochemical pathways characterizing PD. These VOCs can be detected by GC–MS combined with solid-phase microextraction (SPME) technique. Three groups of rats were studied: DA-lesioned rats injected with 6-hydroxydopamine (HDA; 250 μg/rat n=11); control rats injected with saline (n=9), and control rats injected with DSP-4 (n=8), a specific noradrenergic neuron toxin. Blood and striatal tissue homogenate were analyzed. In the blood, 1-octen-3-ol and 2-ethylhexanol were found at significantly higher concentrations in HDA versus sham rats. In the striatal homogenate 1-octen-3-ol and other four compounds were found at significantly lower concentrations in HDA versus sham rats. 1-Octen-3-ol is a cytotoxic compound. These results may lead to the development of an early diagnostic test for PD based on profiling of VOCs in body fluids.

Break: Lunch Break 13:10-14:00 @ Restaurant

Kazumasa saigoh

Kinki University, Japan

Title: The concentration of oxidized DJ-1 protein (oxDJ-1) in red blood cells is useful for the diagnosis method of Parkinson\\\'s disease

Time : 14:00-14:30

Biography:

Kazumasa Saigoh, M.D., Ph.D. born in Osaka, Japan. He had medical and graduate training at the Kinki University Faculty of Medicine Department of Neurology and received his PhD in 1999. He worked Post-doc at the National Center of Neurology and Psychiatry of Japan. He specialized in Neurogenetics and Circadian rhythm in 2000-2003 at the Howard Hughes medical institute in University of Utah. In 2004, he give a position as Lecturer of Kinki University Faculty of Medicine, teaching Neurogenetics and Neurology. In 2015, He served concurrently as Associate professor at the Kinki University Faculty of Science and Engineering, Department of Life Science.

Abstract:

Parkinson disease (PD) are the most common neurodegenerative disorders. Although PD diagnosis is difficulty among Progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and PD. Examination of biomarkers of Parkinson’s disease PD usually focuses on the factors in the cerebrospinal fluid, and there are very few reports on simple biomarkers identified by blood analysis. We determined the level of oxidized DJ-1 protein (oxDJ-1) in red blood cells by the ELISA method. The level of oxDJ-1 was 124.07 ± 13.7 ng oxDJ-1/mg protein in 43 un-treated PD patients group; 88.0 ± 29.8 ng oxDJ-1/mg protein in 9 PSP patients group and 98.8 ± 13.9 ng oxDJ-1/mg protein in 5 MSA patients group. The mean level in 17 control group was 56.0 ± 6.2 ng oxDJ-1/mg protein, showing significant intergroup differences. The clinical courses after intervention with L-dopa treated PD showed a tendency toward decreasing oxDJ-1 levels in the same patient. Our results showed that measurement of oxDJ-1 levels in red blood cells is useful and oxDJ-1 can be used as a biomarker for the early diagnosis of Parkinson’s disease.

Session Introduction

Dasiel O Borroto-Escuela

Karolinska Institutet, Sweden

Title: On the role of A1-D1 heteroreceptor complexes in the direct pathway in models of Parkinson’s disease

Time : 14:30-16:00

Biography:

Dasiel O Borroto-Escuela has completed his PhD from Polytechnic University of Catalonia, Spain. Since 2009, he has been a Contracted Postdoctoral Researcher at the Department of Neuroscience, Karolinska Institutet. His primary focus is on understanding whether alterations in specific heteroreceptor complexes and if their receptor-receptor interactions are associated with and/or play a role in pathogenetic mechanisms contributing to brain disease development, inter alia Parkinson’s disease, schizophrenia, addiction and depression. He has received a significant number of awards, among which are the UPC Excellence Thesis Award, the FEBSYSF 2013, the ECNP 2014 Fellow Award. He has published over 70 papers in neuroscience in the last five years. His major achievements involve pioneering work on understanding the molecular integration of signals in the brain via receptor-receptor interaction in heteroreceptor complexes and its functional effects also, in the implementation of new innovative tools and screening technologies to identify GPCR oligomers.

Abstract:

Among a large number of behavioural studies on adenosine A1-Dopamine D1 receptor interactions, a few examples may be given. Thus, the A1 receptor agonist CPA counteracted the D1 receptor agonist (SKF 38393)-induced grooming behavior and counteracted dyskinetic behavior in rabbits. In line with these results, the A1 receptor antagonist CPT enhanced the motor activating effects of the D1 agonist SKF 38393 in reserpinized mice and in rat models of Parkinson’s disease (unilateral 6-OH-dopamine lesions of the nigrostriatal dopamine pathway). This behavioural result at the network level indicates the existence of antagonistic A1-D1 receptor interactions. The molecular basis of the antagonistic A1-D1 receptor interaction likely involves the existence of A1-D1 heteroreceptor complexes in the direct pathway. The A1-D1 heteroreceptor complexes may reflect a direct physical interaction without the involvement of an adapter protein, since specific BRET and FRET signals can be detected between fluorescent-tagged A1 and D1 receptors upon transient co-transfection in cell lines. Furthermore, in situ Proximity Ligation Assay clearly demonstrated that A1 and D1 receptors exist as heteroreceptor complexes in rat brain. Antagonistic A1-D1 interactions also exist at the level of the second messengers. These results suggest a role of A1 receptor agonists and antagonists in the treatment of Parkinson’s disease with dysfunction of D1 receptor signaling via their actions on the A1-D1 heteroreceptor complexes located in the direct pathway. A1 agonists may, for example, reduce levodopa induced dyskinesias. It will be of substantial interest to know how the A1-D1 receptor interaction may regulate trophic mechanisms such as neurotrophic factors and neuronal differentiation.

Break: Coffee Break 16:00-16:30 @ Foyer

Chair

Michael Ugrumov

Institute of Developmental Biology RAS, Russia

Session Introduction

Eman Khedr

Assiut University, Egypt

Title: Prevalence of Parkinson’s disease in Egypt: A review of community-based survey

Time : 16:30-17:00

Biography:

Eman M Khedr has done her Post-Doctorate Training course in Neurophysiology in Gentoft Hospital, Copenhagen (Denmark) 1998 supervised by Professor Fredrekson; and a training course for diagnosis and management of Parkinson Disease Patients in Oregon University Hospital (Portland) 2000, supervised by Professor John Nutt. She achieved a Postdoctoral Fellowship to study methods of measuring cortical excitability in different diseases for 3 months in Sobell Department of Motor Neuroscience and Movement Disorders, National Hospital for Neurology and Neurosurgery, Queen Square, London.

Abstract:

Introduction: There are few community-based studies of Parkinson’s disease (PD) from Arabic countries; 4 of them have been performed in Egypt. Such studies are more informative than hospital-based data in countries with a large rural population such as Egypt where people may not be able to come to hospital for treatment. Material & Methods: A systematic search of Medline and Global Health for original population-based studies on Parkinson’s disease was conducted. We found only 4 community-based studies that were done in different Egyptian governorates including, Assiut, Al Kharga, Al Quseir and Qena. Results: Overall the recorded Crude Prevalence Rate (CPR) of Parkinson’s disease in Egypt was varied in different governorates and ranged from 53 to 557/105 inhabitants (all ages) and the CPR of PD ranging from 213.15 to 2748/105 among the population aged >40 or >50 years. The crude incidence rate was ranging from 82-62/105 (all ages) with male to female ratio 4:1. The highest age-specific CPR was recorded among subjects >75 years old. The CPR showed a tendency to be higher in males than females and in industrial than non-industrial areas. There was a significantly higher CPR among illiterate than literate persons. About one quarter of patients had cognitive impairment (14.3-22.3%). All cases had positive symptoms in at least one or more NMS Domains. Conclusion: The overall prevalence of PD disease is high in Nile Valley governorates of Upper Egypt compared to other Arabic countries.

Ashton Rogers

The University of the West Indies, West Indies

Title: The effect of systemic inflammation induced by a high sucrose diet on inflammation in the rat substantia nigra

Time : 17:00-17:30

Biography:

Ashton Rogers, the first person in the English speaking Caribbean to be awarded a PhD in Neuroscience by The University of the West Indies, is very enthusiastic about better understanding the relationship between diet, metabolic syndrome and neuroinflammation in the substantia nigra. After graduating in 2014, he founded the first Neuroscience Centre of Trinidad and Tobago, a non-profit organization aimed at promoting brain health awareness and improving the welfare of patients affected with neurological diseases. He is presently establishing the first Neuroscience Foundation of Trinidad and Tobago, a charity organization to sponsor patients in need of foreign treatment.

Abstract:

Animal studies robustly demonstrate that systemic inflammation evoked by bacterial endotoxin can potentiate inflammation in the brain through the activation microglial cells. However, it is unclear if systemic inflammation associated with Metabolic Syndrome (MetS) can affect neuroinflammation in the Substantia Nigra (SN). MetS is primarily caused by obesity due to a high sucrose diet. The objective of this research is to determine if systemic inflammation induced by a high sucrose diet can affect an ongoing inflammatory process in the rat SN. Sprague Dawley rats were given a stereotaxic intranigral injection of either a normal dose (2.0 μg, n=40) or a low dose (0.2 μg, n=40) of Lipopolysaccharide (LPS) to trigger a high level or benign inflammatory process, respectively. The groups were then sub-divided and provided with either normal drinking water or drinking water with 30% sucrose (w/v) for 30 days. All rats were fed standard rat chow. Immunocytochemistry was used to assess morphological changes of microglial cells, astrocytes and dopamine neurons in the SN. Real-time RT-PCR was used to assess an array of pro and anti-inflammatory markers in the SN, adipose tissue and liver. The results show that the sucrose-fed rats exhibited a higher level of neuroinflammation in the SN. Interestingly, the group injected with the low dose of LPS and provided with sucrose displayed the highest level of inflammation. These findings support the hypothesis that a high sucrose diet and the resulting systemic inflammation can exacerbate a benign inflammatory process in the SN, thus increasing the risk of developing PD.