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1029 Screening of neuroprotective drugs by up-regulation of neurotrophic factor synthesis in cultured mouse astrocytes
Poster Abstracts salsolinol group. However in the control group three-time increase of mean frequency (p < 0.01) was observed during GD whereas in the salsolinol injected alfimals the fiequency of vagal discharges during distension renlained unchanged (p - 0.4). Conclusion: Our study revealed lack o f V A A fiequency response to GD in the rats injected with salsolinol. These results suggest peripheral defect of the sensory part ofvago-vagal reflexes in experimental PD rats. 1027 Cardiac Autonomic Function in Patients with Idiopathic Parkinson's Disease Krygowska- Wajs, A 2, Furgala, A 1, Dobrek, L 1, Thor, pjZ.
1Department of Pathophysiology, Collegium Medieum, Jagiellonian University, Cracow, Poland," :Department of Neurology, Collegium Ivledieum, Jagiellonian University, Cracow, Poland Background: Cardiovascular autonomic reflex tests have a limited view of the overall autonomic cardiac control mechalfisms in idiopathic Parkinson's disease (IPD). The heart rate variability (HRV) is a useful non-invasive test to assess autonomic tonic cardiovascular regulation. This study was designed to evaluate autonomic tonic cardiovascular activity in IPD. Methods: Fifty patients with LPD and fifty controls were included in the study. Patients were divided into two groups: A early stage IPD and B-advanced IPD. In all investigated groups H R V was measured at 5 rain at rest and during deep breathing test (DB).The blood pressure in isometric hand grip test (IHG) was measured subsequently for 1, 3, 5 minute during the test and after the test. Results: HRV: in both patients groups low frequency (LF) and tfigh frequency (HF) signal power were lower than in control measured in the rest as well as in DB test. There were no differences between two groups of patients. The changes of diastolic and systolic blood pressure in response to isometric hand grip test (IHG) were reduced in both patients groups. Conclusion: The results of our study indicate cardiovascular autonomic dysfmlction in the early and advanced IPD patients, despite differences in the stage o f disease. The primary degenerative process in the autonomic nervous system may be responsible for these effects. HRV is a useful non-invasive test to assess autonomic cardiovascular regulation in IPD. 1028 Tile Subthalanlic Region is Active During Emotional Processing in Patients with Paxkinson's Disease
Andrea A. Kiihn, L3, MarwanHariz, L2, Paul Silberstein, a, Steve Tisch, a':, Andreas Kupsch 3 , Gerd-Helge Schneider4, Patricia Limousin, L2, Kielan Yarrow, ~ , Peter Brown ~. ~Sobell Department of Motor
Neuroscience arm 3~fovement Disorders and; 2Unit of ffunctional Neurosurgery, Institute of Neurology, London, UK,"aDepartment of Neurology and 4Department of Neurosurgery, Charitd Campus Virchow, Humboldt University, Berlin, Germany High frequency stimulation (HFS) of the subthalamic nucleus (STN) is an efficacious treatment for motor symptoms in PD patients. In some patients however, stimulation may be accompanied by behavioural side effects drawing attention to a possible influence o f HFS on limbic circuits within the STN area. To elucidate the involvement of the human STN region in the processing of emotional information, we investigated changes in oscillatory activity within the STN area in response to emotionally arousing visual stimuli. Local field potentials (LFP) were recorded through deep brain macroelectrodes from the STN area in 10 PD patients during ls presentation of pleasant and unpleasant emotionally arousing and neutral pictures. Data were digitally pass band filtered in the alpha range (8-12Hz), squared and responses averaged across stimulus onset. Changes in alpha activity were defined as the percentage decrease (event related desynchronJzation ERD) or increase in band power during the test interval (0.5s to 3s post-stimuhis) in comparison to the baseline period
Wednesday, November 9, 2005
$361
(2s before stimulus presentation) for each emotional category. A significant ERD of alpha activity was revealed for all stimulus categories starting at about 0.5s after stimulus presentation. However, 1-2s post-stinmhis the ERD was siglfificantly larger in trials of pleasant (nlean ERD 21.6% ± 2.8; p < 0.009) and unpleasant (mean ERD 15.0% d_ 4.2; p - 0.018) compared to neutral stinmli (nlean ERD 4.4% ± 4.2). The findings suggest that the delayed modulation of alpha activity recorded from the STN area in PD may reflect the processing or transmission of information related to emotional stimuli. 1029 Screening of Neuroprotective Drugs by Up-regulation of Neurotxoptlic Factor Synthesis in Cultured Mouse AstrocTtes
Kuno, S, 1'2, Ohta, K:, Mizuta, I:, Fujinami, A 3, Ohta, M :'3. 1Musashi
Hospital, National Center of Neurology and Psychiatry, Tokyo, )'apart," 2Utano Hospital, National Hospital Organization, Kyoto, Japan; aKobe Pharmaceutical University, Kobe, Japan Objective: We developed a sensitive and simple system for screening neuroprotective drugs in cultured mouse astrocytes. Using this system, we examined whether doparnine agonists, apomorphine and cabergoline, and alltiexcitotoxic agent, riluzole, may stinmlate protein and m R N A expressions o f N G F , BDNF and GDNF. Background: Neurodegeneration in Parkinson's disease may result from a reduction of neurotrophins in the nigrostriatal region. Upregulation of endogenous neurotrophic factors would then exert neuroprotective effects. Method: Astrocytes were prepared from passaged cell cultures of whole brain of 8-day-old ICR nfice. Enzyme-linked inmlunosorbent assay for NGF, B D N F and G D N F measured directly in the culture mediunl, and Northern blot analysis and RT-PCR for m R N A were performed. Results: Apomorphine, a D~/D: dopamine agonist, elevated N G F and G D N F levels in the cultured medium 122-fold and 1.8-fold of the control at 24h, respectively. By treatment with cabergoline, a Dz/weak Da agonist, N G F and G D N F contents elevated rapidly and reached to 78-fold and 9-fold at 24 h, respectively. Treatment with riluzole elevated NGF, BDNF and G D N F levels to 109-fold, 2.0-fold and 3.1-fold at 24h. Relative levels of these m R N A s indicated that increases of these proteins are due to gene expression. Condusiom Dopanfine agonists, apomorplfine and cabergoline, and riluzole stinlulate protein and m R N A expressions of N G F and G D N F and/or BDNF in cultured mouse astrocytes. G D N F may be a useful therapeutic target in view of its marked neurotrophic effects on doparninergic neurons. 1030 Genetic Analysis ol LLRRK2 Mutations in Patients with ParIdnson's Disease
Deng, H l, Le, W ~, G u t , y.2, Hunter, C ~, Xie, W ~, Janko vic, J~. 1Baylor
College of Medicine, Houston, United States of America; :Central South University, Changska, P.R China Parkinson's disease (PD) is one o f the most common progressive neurodegenerative disorders characterized by bradykinesia, rigidity, resting tremor, and postural instability. Recently, R1396G and G2019S mutations in leucine-rich repeat kinase 2 (LRRK2) gene were reported to be the most frequent mutations accounting for genetically determined PD in patients from the Basque region of Spain and general European population. We conducted nlutation analysis of R1396G and G2019S in 486 PD patients from North America. One 53-year old Hispanic female patient who has a five-year history of progressive P D complicated by levodopa-related motor fluctuations and dyskinesias was found to have LRRK2 R1396G mutation. This is the first case of PD identified with R1396G mutation in North America. Six other cases including 5 Caucasians and 1 Hispanic, were found to have LRRK2 G2019S mutation. Age at onset in these patients was 43-75 years (mean 56 years). The clinical features
1Department of Pathophysiology, Collegium Medieum, Jagiellonian University, Cracow, Poland," :Department of Neurology, Collegium Ivledieum, Jagiellonian University, Cracow, Poland Background: Cardiovascular autonomic reflex tests have a limited view of the overall autonomic cardiac control mechalfisms in idiopathic Parkinson's disease (IPD). The heart rate variability (HRV) is a useful non-invasive test to assess autonomic tonic cardiovascular regulation. This study was designed to evaluate autonomic tonic cardiovascular activity in IPD. Methods: Fifty patients with LPD and fifty controls were included in the study. Patients were divided into two groups: A early stage IPD and B-advanced IPD. In all investigated groups H R V was measured at 5 rain at rest and during deep breathing test (DB).The blood pressure in isometric hand grip test (IHG) was measured subsequently for 1, 3, 5 minute during the test and after the test. Results: HRV: in both patients groups low frequency (LF) and tfigh frequency (HF) signal power were lower than in control measured in the rest as well as in DB test. There were no differences between two groups of patients. The changes of diastolic and systolic blood pressure in response to isometric hand grip test (IHG) were reduced in both patients groups. Conclusion: The results of our study indicate cardiovascular autonomic dysfmlction in the early and advanced IPD patients, despite differences in the stage o f disease. The primary degenerative process in the autonomic nervous system may be responsible for these effects. HRV is a useful non-invasive test to assess autonomic cardiovascular regulation in IPD. 1028 Tile Subthalanlic Region is Active During Emotional Processing in Patients with Paxkinson's Disease
Andrea A. Kiihn, L3, MarwanHariz, L2, Paul Silberstein, a, Steve Tisch, a':, Andreas Kupsch 3 , Gerd-Helge Schneider4, Patricia Limousin, L2, Kielan Yarrow, ~ , Peter Brown ~. ~Sobell Department of Motor
Neuroscience arm 3~fovement Disorders and; 2Unit of ffunctional Neurosurgery, Institute of Neurology, London, UK,"aDepartment of Neurology and 4Department of Neurosurgery, Charitd Campus Virchow, Humboldt University, Berlin, Germany High frequency stimulation (HFS) of the subthalamic nucleus (STN) is an efficacious treatment for motor symptoms in PD patients. In some patients however, stimulation may be accompanied by behavioural side effects drawing attention to a possible influence o f HFS on limbic circuits within the STN area. To elucidate the involvement of the human STN region in the processing of emotional information, we investigated changes in oscillatory activity within the STN area in response to emotionally arousing visual stimuli. Local field potentials (LFP) were recorded through deep brain macroelectrodes from the STN area in 10 PD patients during ls presentation of pleasant and unpleasant emotionally arousing and neutral pictures. Data were digitally pass band filtered in the alpha range (8-12Hz), squared and responses averaged across stimulus onset. Changes in alpha activity were defined as the percentage decrease (event related desynchronJzation ERD) or increase in band power during the test interval (0.5s to 3s post-stimuhis) in comparison to the baseline period
Wednesday, November 9, 2005
$361
(2s before stimulus presentation) for each emotional category. A significant ERD of alpha activity was revealed for all stimulus categories starting at about 0.5s after stimulus presentation. However, 1-2s post-stinmhis the ERD was siglfificantly larger in trials of pleasant (nlean ERD 21.6% ± 2.8; p < 0.009) and unpleasant (mean ERD 15.0% d_ 4.2; p - 0.018) compared to neutral stinmli (nlean ERD 4.4% ± 4.2). The findings suggest that the delayed modulation of alpha activity recorded from the STN area in PD may reflect the processing or transmission of information related to emotional stimuli. 1029 Screening of Neuroprotective Drugs by Up-regulation of Neurotxoptlic Factor Synthesis in Cultured Mouse AstrocTtes
Kuno, S, 1'2, Ohta, K:, Mizuta, I:, Fujinami, A 3, Ohta, M :'3. 1Musashi
Hospital, National Center of Neurology and Psychiatry, Tokyo, )'apart," 2Utano Hospital, National Hospital Organization, Kyoto, Japan; aKobe Pharmaceutical University, Kobe, Japan Objective: We developed a sensitive and simple system for screening neuroprotective drugs in cultured mouse astrocytes. Using this system, we examined whether doparnine agonists, apomorphine and cabergoline, and alltiexcitotoxic agent, riluzole, may stinmlate protein and m R N A expressions o f N G F , BDNF and GDNF. Background: Neurodegeneration in Parkinson's disease may result from a reduction of neurotrophins in the nigrostriatal region. Upregulation of endogenous neurotrophic factors would then exert neuroprotective effects. Method: Astrocytes were prepared from passaged cell cultures of whole brain of 8-day-old ICR nfice. Enzyme-linked inmlunosorbent assay for NGF, B D N F and G D N F measured directly in the culture mediunl, and Northern blot analysis and RT-PCR for m R N A were performed. Results: Apomorphine, a D~/D: dopamine agonist, elevated N G F and G D N F levels in the cultured medium 122-fold and 1.8-fold of the control at 24h, respectively. By treatment with cabergoline, a Dz/weak Da agonist, N G F and G D N F contents elevated rapidly and reached to 78-fold and 9-fold at 24 h, respectively. Treatment with riluzole elevated NGF, BDNF and G D N F levels to 109-fold, 2.0-fold and 3.1-fold at 24h. Relative levels of these m R N A s indicated that increases of these proteins are due to gene expression. Condusiom Dopanfine agonists, apomorplfine and cabergoline, and riluzole stinlulate protein and m R N A expressions of N G F and G D N F and/or BDNF in cultured mouse astrocytes. G D N F may be a useful therapeutic target in view of its marked neurotrophic effects on doparninergic neurons. 1030 Genetic Analysis ol LLRRK2 Mutations in Patients with ParIdnson's Disease
Deng, H l, Le, W ~, G u t , y.2, Hunter, C ~, Xie, W ~, Janko vic, J~. 1Baylor
College of Medicine, Houston, United States of America; :Central South University, Changska, P.R China Parkinson's disease (PD) is one o f the most common progressive neurodegenerative disorders characterized by bradykinesia, rigidity, resting tremor, and postural instability. Recently, R1396G and G2019S mutations in leucine-rich repeat kinase 2 (LRRK2) gene were reported to be the most frequent mutations accounting for genetically determined PD in patients from the Basque region of Spain and general European population. We conducted nlutation analysis of R1396G and G2019S in 486 PD patients from North America. One 53-year old Hispanic female patient who has a five-year history of progressive P D complicated by levodopa-related motor fluctuations and dyskinesias was found to have LRRK2 R1396G mutation. This is the first case of PD identified with R1396G mutation in North America. Six other cases including 5 Caucasians and 1 Hispanic, were found to have LRRK2 G2019S mutation. Age at onset in these patients was 43-75 years (mean 56 years). The clinical features