3.318 D3 DOPAMINE RECEPTOR FACILITATES INFILTRATION OF CD4+ T-CELLS AND NEURODEGENERATION OF SUBSTANTIA NIGRA IN A MOUSE MODEL OF PARKINSON'S DISEASE

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Results: Significant increase in counts of contralateral rotation was observed in the rats cotreated with 6-OHDA/BAb in comparing with the other two control groups. In addition, significantly decrease in TH immunoreactive neurons in the SN was found in animals treated with 6-OHDA/BAb compared with 6-OHDA/CAb or 6-OHDA/Veh groups. Furthermore, significantly increased microglia activation was found to be concomitant with dopaminergic neurodegeneration. Finally, induction of proinflammatory cytokines was significantly enhanced in the SN from combined treated animals. Conclusions: This study showed that deficits in CD200-CD200R system exacerbated dopaminergic neurodegneration and microglial activation in 6-OHDA-lesioned model of PD. Our results suggest that CD200-CD200R signalling dysfunction may be involved in the aetiopathogenesis of PD. 3.315 EFFECTS OF INTRAVENTRICULAR TRANSPLANTATION OF BONE MARROW STEM CELLS ON BEHAVIOR AND COGNITION IN 6-OHDA LESIONED RATS P. Gu1,2 , Z.-X. Zhang1,2 , D.-S. Cui1,2 , Y.-Y. Wang1,2 , M.-W. Wang1,2 . 1 Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, 2 Department of Neurology, First Hospital of Hebei Medical University, Shijiazhuang, China Objective: To observe the behavior and cognition of Parkinson disease (PD) model rats treated with 6-hydroxydopamine (6-OHDA) and assess the effects of Bone Marrow Stromal cells (BMSCs) intracerebroventricular transplantation on the behavior and cognition of them. Methods: 6-OHDA was injected stereotaxically into substantia nigra compact and ventral tegmental area of SD rats to make PD model. The successful PD model rats were randomly divided into BMSCs group, PBS group and model group, then the Morris water maze test was did. BMSCs (10 ml, 1.0×105 /ml) and the same volume of phosphate buffer solution were injected stereotaxically into the right lateral cerebral ventricle of BMSC group and PBS group respectively. APO-induced rotation behavior, the Morris water maze test and the detection of BMSCs by immunohistochemistry had been done before and/or after transplantation. Results: After transplantation, the APO-induced rotation times of rats in BMSCs group decreased significantly (P < 0.05). In the Morris water maze test, the escape latency of rats in BMSCs group was significantly decreased (P < 0.05); the crossing times, percentage of swimming distance and swimming time in the platform quadrant were increased. BrdU-immunoreactive positive cells were seen at the transplanted area and migrated to the surrounding areas of lateral cerebral ventricle. Conclusion: The intracerebroventricular transplantation of BMSCs could survive and migrate and greatly improve the behavioral and cognitive function of PD model rats made by injection of 6-OHDA. 3.316 LMX1B CAN PROMOTE DOPAMINERGIC NEURONS DIFFERENTIATION FROM EMBRYONIC STEM CELLS L.-P. Tian, S. Zhang, Y.-J. Zhang, J.-Q. Ding, S.-D. Chen. Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China Dopaminergic neurons differentiation is essential before embryonic stem cells (ESC) transplantation in Parkinson’s disease. Manipulating exogenous genes expression was an effective strategy for dopaminergic neurons induction from ESC. Lmx1b is a key transcription factor during midbrain dopaminergic neurons development. In the present study, we found endogenous lmx1b expression was induced during dopaminergic neurons differentiation from embryonic stem cells. And then, we used lentivirus system to deliver exogenous lmx1b into ESC to investigate the potential to differentiate into dopaminergic neurons. By

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serum free neural induction, the tyrosine hydroxylase positive dopaminergic neurons increased from 18% of total differentiated cells to nearly 50% after exogenous lmx1b over-expression in R1 cells, and this effect was accompanied by increased dopamine uptake. This work presented a novel dopaminergic neurons differentiation approach. 3.317 THE SIMULATED MICROGRAVITY ENHANCES THE DIFFERENTIATION OF MESENCHYMAL STEM CELLS INTO NEURONS J. Chen. The Fourth Military Medical University, Xi’an, China Growing evidence shows that physical microenvironments and mechanical stresses, independent of soluble factors, help influence mesenchymal-stem-cell fate. rMSCs present spread, spindle shape when cultured in normal gravity (NG) while in simulated microgravity (SMG) they become unspread, round shape. Here we demonstrate that simulated microgravity can enhance the differentiation of mesenchymal stem cells into neurons, which might be a new strategy for the treatment of central nervous system diseases. rBMSCs were cultured respectively in normal gravity and in a clinostat to simulate microgravity, followed with neuronal differentiated medium. The neuronal cells derived from rMSCs in SMG express higher MAP-2, TH and CHAT. Furthermore, as rMSCs are subjected to SMG, they excrete more neurotrophins like NGF, BDNF and CNTF. Neuronal cells from SMG group generated more mature action potentials and displayed repetitive action potentials by comparison to cells from NG group. We get the conclusion that simulated microgravity can enhance the differentiation of mesenchymal stem cells into neurons. 3.318 D3 DOPAMINE RECEPTOR FACILITATES INFILTRATION OF CD4+ T-CELLS AND NEURODEGENERATION OF SUBSTANTIA NIGRA IN A MOUSE MODEL OF PARKINSON’S DISEASE H. Gonzalez Velozo1 , C. Prado Terrazas2 , R. Pacheco Rivera2 . 1 Andres Bello University, Fundacion Ciencia Para La Vida, 2 Fundacion Ciencia Para La Vida, Santiago, Chile Emerging evidence has demonstrated that CD4+ T-cells infiltrate in the substantia nigra (SN) of Parkinson’s disease (PD) patients which strongly contribute to neurodegeneration of dopaminergic neurons. Moreover, CD4+ T-cells can interact with microglia regulating their phenotype/function, these cells may maintain homeostasis and support the neuronal growth or alternatively promote neuronal dead in the central nervous system. Importantly, dopamine receptors have been described in CD4+ T-cells, where they can regulate diverse cellular processes. The purpose of this study was to determine the impact of dopamine D3 receptor in the brain infiltration of CD4+ T-cells, microglia activation and neurodegeneration of dopaminergic neurons in the SN during PD using a rodent model. Accordingly, we analyzed dopamine receptors expression by flow cytometry and RT-PCR. Results show that functional dopamine receptor D3 is expressed on naïve and activated CD4+ T-cells. Stimulation by the selective agonist PD128907 promoted a decreased production of forskolin-induced cAMP. In vivo experiments show that lack of dopamine receptor D3 protects from 1-methyl-4-phenyl-1,2,3,6-tertahydropyridine (MPTP)-induced neurodegeneration of dopaminergic neurons in the SN. Furthermore, absence of dopamine receptor D3 was associated with significant reduction on brain-infiltration of CD4+ T-cells and attenuated microgliosis. This data indicate that dopamine receptor D3 expressed in CD4+ T-cells is functional. Moreover, dopamine receptor D3 contributes to CD4+ T-cells infiltration in the SN, microgliosis and neurodegeneration of dopaminergic neurons during PD. These observations add new insights in our understanding of the

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mechanism by which CD4+ T-cell contribute to neurodegeneration during PD and suggest a novel target for therapeutic intervention. 3.319 DEEP BRAIN STIMULATION AND ON-LINE EXECUTIVE CONTROL IN PARKINSON’S DISEASE T. Hasbroucq1 , F. Fluchere ` 2 , F. Vidal1 , B. Burle1 , J.-P. Azulay2 . 1 Neurobiologie de la Cognition, CNRS and Aix-Marseille Universit´e, 2 Neurologie et Pathologie du Mouvement, CHU Timone, Marseille, France We evaluated the effects of high frequency deep brain stimulation (DBS) on the faculty to detect, inhibit and correct erroneous responding in Parkinson’s disease (PD) patients. High frequency DBS is generally considered to inactivate the subthalamic nuclei (STN) and to restore the thalamo-cortical projections impaired by striatal dopamine depletion caused by PD. This therapy dramatically improves PD motor symptoms. Recent fMRI data collected in healthy volunteers suggest that the STN are involved in the urgent inhibition of ongoing actions. We reasoned that a side effect of DBS could be to impair this ability in PD patients. Sixteen PD patients treated by DBS fperformed a conflict reaction time (RT) task. The electromyographic activity of the response agonists (flexor pollicis brevis) was recorded and analysed, allowing the detection of partial errors, that is of subliminal activations of the muscles involved in erroneous responses. DBS shortened correct RT but increased the overt error rate and decreased the number of partial errors. Detailed analyses of the temporal distribution of the responses revealed that the increase in overt error rate observed when the stimulator was ON was specifically due to a failure to detect, inhibit and correct partial errors before they resulted in overt erroneous responses. Our data suggest that while it improves motor performance by shortening RT, DBS impairs the patients’ faculty to suppress erroneous response activations as revealed by their inability to counteract partial errors when the stimulator was ON. 3.320 INSIGHTS INTO THE MECHANISM OF PARADOXICAL KINESIA FROM SUBTHALAMIC NUCLEUS RECORDINGS IN PARKINSON’S DISEASE A. Anzak1,2 , A. Pogosyan1,2 , H. Tan1 , T. Foltynie2 , P. Limousin2 , L. Zrinzo2 , M. Hariz2 , K. Ashkan3 , W. Thevathasan1 , M. Bogdanovic1 , A. Green1 , T. Aziz1 , P. Brown1 . 1 Department of Clinical Neurology, University of Oxford, Oxford, 2 Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology & The National Hospital for Neurology & Neurosurgery, 3 Department of Neurosurgery, Kings College Hospital, London, UK Objective: Paradoxical Kinesia (PK) describes the brief, but dramatic, normalisation of motor activity in patients with Parkinson’s disease (PD) in highly arousing situations. We sought electrophysiological evidence for arousal in PK and changes in induced activity in the basal ganglia potentially mediating the phenomenon. Methods: Local field potentials (LFPs) were recorded from bilateral deep brain stimulation (DBS) electrodes implanted in the subthalamic nuclei (STN) of 10 patients with PD, whilst ‘off’ and ‘on’ dopaminergic medication. Patients gripped a force dynamometer as quickly and strongly as possible in response to visual (V) or auditory-visual (AV) cues, the latter of which involved delivery of a 96dB auditory stimulus simultaneous with the V cue, in ~50% of randomly selected trials. Results: Patients exhibited significant (P < 0.05) improvements in reaction time and peak rate of development of force in response to AV as compared to V cues, independent of dopaminergic state. Simultaneous LFP recordings revealed a short latency evoked potential with a similar morphology and latency to the P50,

believed to be a hallmark of arousal and to have its origin in the reticular activating system (RAS). This STN P50 was larger in AV trials and independent of dopaminergic state. Increases in induced high gamma (60–90 Hz) power were further observed with AV cueing. Elevations in STN gamma power have previously been associated with improved motor performance in PD. Conclusions: Future manipulation of the electrophysiological hallmarks contributing to motor improvement in PK, may lead to more specific and targeted forms of DBS for PD. 3.321 THE RELATIONSHIP OF TAU ACETYLATION AND TAU PHOSPHORYLATION IN ALZHEIMER’S DISEASE L. Tan, L. Zhu, H. Tang, Z. Wang, X. Wang. Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Introduction: As we all known, aberrant accumulation of unbound hyperphosphorylated insoluble tau as neurofibrillary tangles (NFTs) is implicated in the pathogenesis of neurodegenerative tauopathies including Alzheimer’s disease. In recent studies, many evidence support the idea that tau protein can be acetylated in vivo and vitro. Thus, tau acetylation and phosphorylation may represent specific modifications required to dynamically regulate tau function. Aim: To expore the mechanism of negative regulation of tau function via acetylation and phosphorylation events. Results: In our work, we found that K395 is an acetylated lysine residue in tau. To identiy this acetylated lysine residue, K→R acetylation mutant were generated and expressed in HEK-293 cells. Western analysis of lysine→arginine mutant demonstrated that mutation of K395 reduced tau acetylation in HEK-293 cells. To evaluate the relationship of tau acetylation and tau phosphorylation, we co-transfected GSK-3 beta, glycogen synthase kinase 3b, one of tau-specific kinases, to induce tau hyperphosphorylation. Interestingly, expression of tau-K395R non-mimetic mutant showed a significant reduction of the phosphorylation level of ps396, a specific site of GSK-3 beta. We speculate that whether tau acetylation facilitates the association of GSK-3 beta and tau. Our next work is to further validate our speculation. Thus, monitoring tau acetylation levels may provide a new therapeutic targeting of Alzheimer’s disease. 3.322 TOXICITY OF ALUMINUM AND ALZHEIMER DISEASE N. Djebli. Department of Biology, Faculty of SNV, University of Mostaganem, Mostaganem, Algeria The continued occurrence of occupational Aluminum overexposure and Aluminum poisoning in the World remains a serious problem despite awareness of its adverse health effects. Urban water supplies may contain a greater concentration because water is usually treated with aluminum before becoming part of the supply. Subsequent purification processes that remove organic compounds take away many of the same compounds that bind the element in its free state, further increasing aluminum concentration. Aluminum is known for its toxicity and was observed by its presence in dialysis fluids in patients with renal failure and drinking water. Among all the organs which Aluminium has its toxic effects, the brain is the most sensitive to these effects. It may also affect brain function by interfering with neurotransmitter release and synapse formation and many different areas of the brain including the cerebral cortex, cerebellum and hippocampus. Aluminium is a potent neurotoxin and has been associated with Alzheimer’s disease (AD) causality for decades. Prolonged aluminium exposure induces oxidative stress and increases amyloid beta levels in vivo