10th World Congress on Neuropharmacology August 28-29, 2018 Paris, France

Yutaka Kuroda, Medicine Doctor, now is an Assistant professor of Department of Orthopaedic surgery, Kyoto university. In 1994, was received the B.E. degree in Economics from Keio university, got medical doctor license at St. Marianna university school of medicine in 1999, and Medicine Doctor's degree (Ph.D.) at Graduate School of Medicine, Kyoto University in 2011. His researches focus on the bone regeneration. A Research Award from “The Japanese Society of Inflammation and Regeneration 2014 and 2016 meeting”. Member of the Japanese Investigation Committee of Health and Welfare on the establishment of guidelines for Osteonecrosis of the femoral-head.

In the past decades, minimally invasive regenerative therapy has been desired for the early stages of osteonecrosis of the femoral head (ONFH). ONFH is common among young people in their 30s and 40s. In the clinic, although patients are diagnosed, 70%–80% of ONFH patients experience femoral head collapse and have to undergo total hip arthroplasty. The purpose of this study was to evaluate the safety and clinical outcomes of inegectable rhFGF-2 gelatin hydrogel. Ten ONFH patients up to precollapse stage 2 underwent a single local administration of 800-μg rhFGF-2 gelatin hydrogel and were followed up for four year. Primary outcomes included adverse events and complications. Secondary outcomes included changes in Harris Hip Scores, VAS pain scores, UCLA scores, radiological changes as determined via X-ray, CT, and MRI images. The surgery was performed with a minimally invasive technique (1 cm of skin incision), and walking was allowed from the day after surgery. Mean clinical scores improved significantly after four years compared with before surgery. There was only one case of femoral head collapse, and it had the greatest necrosis volume fraction and was considered to be in the early collapse stage at the time of operation. The other nine cases did not involve ONFH stage progression, and collapse was prevented. CT and MRI images confirmed bone regeneration in the ONFH. Our research is ongoing, further phase II multiple center study has been started in January 2016.

Ye-Ji Yoon has graduated Kyung Hee University College of Korean Medicine and is in Residency training at Kyung Hee University Hospital at Gangdong, Department of Korean Rehabilitation Medicine.

The objective of this study was to investigate the role of lumbar paraspinal muscles (PSMs) in the progression of different types of spondylolisthesis by examining the correlation between lumbar PSM cross-sectional area (CSA) and slip percentage (SP) in degenerative spondylolisthesis (DS) and isthmic spondylolisthesis (IS). A multicenter retrospective analysis was carried out including 219 subjects diagnosed with lumbar spondylolisthesis. The DS group had 125 subjects and the IS group had 94 subjects. Using T2-weighted axial MRI images, CSAs of the psoas major (PM), multifidus (MU), and erector spinae (ES) were measured and divided by L5 vertebral body (VB) CSA to eliminate biases arising from the physical build of subjects. SP was measured using sagittal T2 weighted images. Correlations between muscle CSA ratio and SP were calculated in each group. Regression analysis was performed to predict the influence of each muscle CSA/VB CSA ratio on SP. No significant correlation was found in the DS group between any of the muscle CSA ratios and SP. Both PM/VB ratio (r=-0.24, p=0.021) and MU/VB ratio (r=-0.26, p=0.012) were negatively correlated with SP in the IS group. MU had more influence on SP than PM in the IS group (regression coefficient MU/VB: -8.08, PM/VB: -4.34). Both PM and MU muscle CSA ratios were negatively correlated with SP in the isthmic group. MU had more influence on SP than PM. No muscles had any correlations with SP in the degenerative group. This discrepancy between the two groups suggests exercise programs or interventions intended to prevent progression of IS and DS should be distinguished in clinical practice.

Xinwang Li has completed his PhD from Capital Normal University. He is a Professor of the Physiological Psychology in Capital Normal University, China. He has published more than 30 papers in reputed journals and Physiological Psychology (teaching material). He has been serving as the Deputy Chairman of the Chinese Committee of Physiological Psychology and an Editorial Board Member of Advances in Psychological Science.

Behavioral sensitization reflects long-term adaptive changes in the central nervous system induced by repeated exposure to drugs of abuse and the process of pathological motivation for drugs or drug-wanting. Previous studies have demonstrated that repeated administration of morphine increased dopamine but decreased acetylcholine in the nucleus accumbens, which included the shell of the nucleus accumbens (NAcS). The present study investigated the effect of balance between the cholinergic and dopaminergic systems in the NAcS on morphine-induced behavioral sensitization. Behavioral sensitization was established by exposure to 5 mg/kg morphine once every three days for a total of three exposures. Expression of behavioral sensitization was challenged by 5 mg/kg morphine. The results showed that: The acetylcholinesterase inhibitor huperzine-A (0.5 μg/side) microinjected into the NAcS blocked initiation and expression of morphine-induced behavioral sensitization, which were reversed by the dopamine D1 receptor agonist SKF38393; The muscarinic receptor antagonist scopolamine (10.8 μg/side) had no effect on morphine-induced behavioral sensitization; We further investigated the role of the M4 receptor in expression of morphine-induced behavioral sensitization because the expression stage is more related to relapse. Microinjection of the M4 receptor agonist LY2033298 (0.2 μg/side), but not the antagonist tropicamide (5, 10, or 20 μM/side), into the NAcS blocked expression of behavioral sensitization; Furthermore, tropicamide (20 μM/side) reversed the inhibition effect of huperzine-A; and SKF38393 (1 μg/side) reversed the inhibitory effect of LY2033298 on expression of morphine-induced behavioral sensitization. Our findings suggest that the balance between dopamine and acetylcholine in the NAcS modulates morphine-induced behavioral sensitization, which can be regulated by the M4 receptor.

Fouad Azizi has completed his PhD in Biophysical Chemistry at the Center of Molecular Biophysics, National Center for Scientific Research (CNRS), Orleans, France. He has a research track of over 20 years working in US universities on projects related to pulmonary diseases and blood disorders. He has published more than 15 papers in reputed journals and presented more than 15 abstracts at prestigious national and international conferences. Currently, he is a Research Scientist, the Director of Electrophysiology Laboratory and the Manager of Confocal Imaging Core at TRI-HMC. His research interests are related to neurosecretion.

GAP-43, called neuromodulin, is a major calmodulin (CaM) and PI (4, 5) P2 binding protein that plays a key regulatory role in synaptic plasticity (e.g. learning and memory). CaM is the Ca2+-receptor for rapid endocytosis (RE) established as the clathrin-independent and dynamin-1-dependent mechanism of vesicle retrieval in adrenal chromaffin cells (ACC). Here, we used patch-clamp recording of whole cell membrane capacitance in ACC to monitor exocytosis coupled to RE in response to pharmacological alteration of GAP-43 and PI (4, 5) P2 levels using anti-GAP-43 antibodies and phenylarsine oxide (PAO) respectively. We found that anti-GAP-43 antibodies and PAO completely blocked RE whereas there was no effect on exocytosis or Ca2+ currents. Inclusion of exogenous CaM, dialyzed into the cell via the whole-cell patch pipette, rescued RE in cells treated with anti-GAP-43 antibodies. Similarly, infusion of PI (4, 5) P2 through the patch pipette was able to rescue RE blockade by PAO though with slower kinetics in comparison to control untreated cells. However intracellular delivery of PI (4, 5) P2 precursor, phosphatidylinositol 4-phosphate (PI4P) failed to restore RE in presence of PAO. In absence of PAO, PI (4, 5) P2 and PI4P potentiated and inhibited respectively RE. Application of the bifunctional thiol dithiothreitol to PAO-treated cells completely prevented the inhibitory effect of PAO on RE. Our data indicate show that: GAP-43 is the prime candidate for regulating free CaM levels required for rapid recycling (RE) of vesicles; PI (4, 5) P2 is directly involved in the signaling (mechanistic) process of RE, probably by facilitating CaM sequestration at endocytic sites for vesicle retrieval.

Yoanna Koedzhikova is currently pursuing her Pharmacy at Faculty of Pharmacy of Medical University of Sofia. She has a long standing interest in Pharmacology and Toxicology and has worked over this scientific project to establish a scientifically important results over the influence of these new chemical compounds on the rat synaptozomes. She also has a deep knowledge in the sphere of preclinical and clinical studies of toxicity.

This study investigate the in vitro effects of newly synthesized hydrazones of N-pirolylcarboxylic acid on isolated rat brain synaptosomes. The main parameters, characterized the functional status of synaptosomes: synaptosomal viability and depletion of reduced glutathione (GSH), were measured. Administered alone, all the compounds (at concentration 50 µM) revealed statistically significant neurotoxic effects on the synaptosomes, compared to the control (non-treated synaptosomes). With lower toxic effects were compound DI5a and DI5g. These compounds (DI5a and DI5g) were examed for possible neuroprotective effects in a model of 6-hydroxydopamine (6-OHDA)-induced oxidative stress. The treatment of isolated rat brain synaptosomes with 6-OHDA is a reliable and commonly used in vitro model for the investigation of processes, which play role in the neurodegenerative disease, including Parkinson’s and Alzheimer’s disease. The mechanism of 6-OHDA neurotoxicity includes the formation of ROS and reactive metabolites, as a result of its metabolism in mitochondria of the neuronal cells. In conditions of 6-OH-dopamine-induced oxidative stress (at concentration 150 μM) on isolated rat synaposomes, DI5a and DI5g (at concentration 50 μM) revealed statistically significant neuroprotective effects by preservation the synaptosomal viability (measured by MTT-test), and GSH deletion, compared to the toxic agent.

Yoanna Koedzhikova is currently pursuing her Pharmacy at Faculty of Pharmacy of Medical University of Sofia. She has a long standing interest in Pharmacology and Toxicology and has worked over this scientific project to establish a scientifically important results over the influence of these new chemical compounds on the rat synaptozomes. She also has a deep knowledge in the sphere of preclinical and clinical studies of toxicity.

This study investigate the in vitro effects of newly synthesized hydrazones of N-pirolylcarboxylic acid on isolated rat brain synaptosomes. The main parameters, characterized the functional status of synaptosomes: synaptosomal viability and depletion of reduced glutathione (GSH), were measured. Administered alone, all the compounds (at concentration 50 µM) revealed statistically significant neurotoxic effects on the synaptosomes, compared to the control (non-treated synaptosomes). With lower toxic effects were compound DI5a and DI5g. These compounds (DI5a and DI5g) were examed for possible neuroprotective effects in a model of 6-hydroxydopamine (6-OHDA)-induced oxidative stress. The treatment of isolated rat brain synaptosomes with 6-OHDA is a reliable and commonly used in vitro model for the investigation of processes, which play role in the neurodegenerative disease, including Parkinson’s and Alzheimer’s disease. The mechanism of 6-OHDA neurotoxicity includes the formation of ROS and reactive metabolites, as a result of its metabolism in mitochondria of the neuronal cells. In conditions of 6-OH-dopamine-induced oxidative stress (at concentration 150 μM) on isolated rat synaposomes, DI5a and DI5g (at concentration 50 μM) revealed statistically significant neuroprotective effects by preservation the synaptosomal viability (measured by MTT-test), and GSH deletion, compared to the toxic agent.