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3.351 THE EFFECTS OF INTRANIGRAL INJECTION OF GHRELIN ON HALOPERIDOL-INDUCED CATALEPSY IN RATS
Wednesday, 14 December 2011 / Parkinsonism and Related Disorders 18S2 (2012) S161–S234
6. Fe2+ significantly produced superoxide (100%, 128% and 163% of control) and iROS (147%, 172% and 231% of control); 7. Fe2+ significantly increased microglial numbers (174%, 208% and 293% of control) and activated microglia, showing enlarged cell bodies and irregular shape. Conclusions: Fe2+ induces selective and progressive dopaminergic neurodegeneration, which is facilitated by microglial activation. 3.348 LEWY PATHOLOGY IS NOT BE THE FIRST SIGN OF DEGENERATION IN SELECTIVELY VULNERABLE NEURONS IN PARKINSON’S DISEASE J. Duda. Parkinson’s Disease Research, Education and Clinical Center, Philadelphia VA Medical Center, Philadelphia, PA, USA Introduction: Incidental Lewy body disease (ILBD) has been postulated to be an intermediate pre-motor condition along the progression of Parkinson’s disease (PD) that might be an ideal situation to examine the early pathology of PD. Objective: To determine if selectively vulnerable neurons demonstrate pathological changes prior to deposition of Lewy pathology (LP) in ILBD. Methods: We examined the extent of nigral dysfunction and degeneration among normal, ILBD and PD cases based on tyrosine hydroxylase (TH) immunoreactivity and neuron densities, respectively. We also examined these measures in the four quadrants of the substantia nigra (SN) in order to further examine regional vulnerability to neurodegeneration and dysfunction in ILBD. Results: ILBD cases have, on average, lower SN neuron densities than normal cases, but the extent of SN degeneration was independent of the distribution of LP in ILBD. Additionally, ILBD cases displayed a significantly higher percentage of TH negative cells in the SN with a clear distinction occurring as early as Braak LB stage 1, prior to the deposition of LP in the nigrostriatal system. Furthermore, neuron density and neuronal dysfunction levels remained constant across Braak stages in ILBD. Conclusions: These results suggest that significant neurodegeneration and cellular dysfunction may precede LP deposition in the SN, challenging the role of LP in the pathogenesis of PD and complicating the relationship between ILBD and PD. 3.349 MIXED LINEAGE KINASE 2 AND HIPPOCALCIN ARE LOCALIZED IN LEWY BODIES OF PARKINSON’S DISEASE M. Nagao, H. Hayashi, S. Matsubara. Tokyo Metropolitan Neurological Hospital, Fuchu, Japan The expression of hippocalcin, a calcium-sensor protein of the recoverin family, and mixed lineage kinase 2 (MLK2) in Lewy bodies (LBs) was immunohistochemically examined in patients with Parkinson’s disease (PD). Hippocalcin and MLK2 were colocalized in the halo of LBs, and neither protein was detected in normal pigmented neurons. Since hippocalcin binds to the C-terminal region of MLK2 [13], it may constitutively activate MLK2. Both hippocalcin and MLK2 may be associated with the pathogenesis of PD. 3.350 STUDIES ON THE PROTECTIVE ROLE OF URIC ACID IN 6-HYDROXYDOPAMINE-INDUCED INJURY OF PC12 CELLS 1
2
1
2
W. Luo , X. Wang . The Department of Neurology, The Department of Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China Objective: To investigate the protective role of uric acid (UA) in the oxidative injury of 6-hydroxydopamine (6-OHDA) on PC12 cells. Methods: The highly differentiated PC12 cells were divided into 4 groups: the control, 6-OHDA, UA and 6-OHDA plus UA. Each of group was subdivided into a further 3 subgroups and cultured
S231
in vitro for 6, 12 and 24 hours respectively. The content of Lactate dehydrogenas (LDH), 8-hydroxy 2’-deoxyguanosine (8OHdG), superoxide dismutase (SOD) in the culture medium and intracellular malondialdehyde (MDA), glutathione (GSH) were detected. Results: The release of LDH and contents of MDA and 8-OHdG in the group treated with 100 mmol·L−1 6-OHDA for 12 and 24 h were significantly increased compared with the control group, while the release of LDH and contents of MDA and 8-OHdG were decreased, which were reversed by 200 mmol/L UA treatment (P < 0.05). The activity of SOD and GSH in cells treated with 100 mmol·L−1 6-OHDA for 12 and 24 h were significantly decreased, which were reversed by 200 mmol·L−1 UA treatment (P < 0.05). Conclusion: These results suggest that UA treatment can prevent PC12 cell from oxidative stress-mediated injury, which may associated with the increased activity of SOD and GSH. 3.351 THE EFFECTS OF INTRANIGRAL INJECTION OF GHRELIN ON HALOPERIDOL-INDUCED CATALEPSY IN RATS L. Shi, H. Jiang, J. Xie. Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Physiology, Medical College of Qingdao University, Qingdao, China Objective: Ghrelin, a natural ligand for the growth hormone secretagogue receptor 1a (GHS-R1a), is mainly secreted from stomach with small amounts produced in the brain. The expression of GHS-R1a in the dopaminergic neurons of substantia nigra (SN) indicates that SN might be a target site of ghrelin. We previously reported that ghrelin could protect dopaminergic neurons through GHS-R1a against neurotoxicity by inhibiting apoptosis, attenuating oxidative stress and enhancing the cell excitability. However, the role of ghrelin in motor coordination is largely unknown. Aim: The present study aims to explore the effects of intranigral injection of ghrelin on haloperidol-induced catalepsy in rats and analyze the dopamine activities in the striatum. Methods: Cannula-embedding technique, intranigral injection, behavior test, High-performance liquid chromatography electrochemical detection (HPLC-ECD) and Fast cyclic voltammetry (FCV) were used. Results: 1. Unilateral microinjection of ghrelin (1000 nmol/L) into the SN induced a contralateral dystonic posturing and attenuate the descent latency in the haloperidol-induced catalepsy rats. 2. Intracerebroventricular injection of ghrelin (1000 nmol/L) increased the dopamine turnover rate and dopamine release electrical stimulated by medial forebrain bundle in the striatum. Conclusion: Ghrelin is capable of attenuating haloperidol-induced catalepsy and regulating the motor function of SN. 3.352 EFFECTS OF GREEN TEA EXTRACT (GTE) ON HALOPERIDOL (HAL) INDUCED NEUROLEPTIC ANXIETY SYNDROME (NAS) AND PARKINSONISM IN RATS T. Malik, D.J. Haleem. Neurochemistry & Biochemical Neuropharmacology Unit, Biochemistry Department, The University of Karachi, Karachi, Pakistan Introduction: HAL elicits NAS along Parkinsonism. HAL induces c-Fos responsiveness in a distributed anxiety-related neural scheme, selected neuronal population of nucleus accumbens. Mood deficits by HAL metabolically effect via diet restriction that reduced body weight. GTE is known to control appetite and body weight while exerting anxiolytic effects. Aim: The current study testifies the hypothesis that GTE may control HAL elicited NAS with reducing Parkinsonism. Methods: Rats (n = 6) were treated with one of the four treatments; oral fluid [water/GTE (1 gm/liter)] plus saline; or oral fluid plus
6. Fe2+ significantly produced superoxide (100%, 128% and 163% of control) and iROS (147%, 172% and 231% of control); 7. Fe2+ significantly increased microglial numbers (174%, 208% and 293% of control) and activated microglia, showing enlarged cell bodies and irregular shape. Conclusions: Fe2+ induces selective and progressive dopaminergic neurodegeneration, which is facilitated by microglial activation. 3.348 LEWY PATHOLOGY IS NOT BE THE FIRST SIGN OF DEGENERATION IN SELECTIVELY VULNERABLE NEURONS IN PARKINSON’S DISEASE J. Duda. Parkinson’s Disease Research, Education and Clinical Center, Philadelphia VA Medical Center, Philadelphia, PA, USA Introduction: Incidental Lewy body disease (ILBD) has been postulated to be an intermediate pre-motor condition along the progression of Parkinson’s disease (PD) that might be an ideal situation to examine the early pathology of PD. Objective: To determine if selectively vulnerable neurons demonstrate pathological changes prior to deposition of Lewy pathology (LP) in ILBD. Methods: We examined the extent of nigral dysfunction and degeneration among normal, ILBD and PD cases based on tyrosine hydroxylase (TH) immunoreactivity and neuron densities, respectively. We also examined these measures in the four quadrants of the substantia nigra (SN) in order to further examine regional vulnerability to neurodegeneration and dysfunction in ILBD. Results: ILBD cases have, on average, lower SN neuron densities than normal cases, but the extent of SN degeneration was independent of the distribution of LP in ILBD. Additionally, ILBD cases displayed a significantly higher percentage of TH negative cells in the SN with a clear distinction occurring as early as Braak LB stage 1, prior to the deposition of LP in the nigrostriatal system. Furthermore, neuron density and neuronal dysfunction levels remained constant across Braak stages in ILBD. Conclusions: These results suggest that significant neurodegeneration and cellular dysfunction may precede LP deposition in the SN, challenging the role of LP in the pathogenesis of PD and complicating the relationship between ILBD and PD. 3.349 MIXED LINEAGE KINASE 2 AND HIPPOCALCIN ARE LOCALIZED IN LEWY BODIES OF PARKINSON’S DISEASE M. Nagao, H. Hayashi, S. Matsubara. Tokyo Metropolitan Neurological Hospital, Fuchu, Japan The expression of hippocalcin, a calcium-sensor protein of the recoverin family, and mixed lineage kinase 2 (MLK2) in Lewy bodies (LBs) was immunohistochemically examined in patients with Parkinson’s disease (PD). Hippocalcin and MLK2 were colocalized in the halo of LBs, and neither protein was detected in normal pigmented neurons. Since hippocalcin binds to the C-terminal region of MLK2 [13], it may constitutively activate MLK2. Both hippocalcin and MLK2 may be associated with the pathogenesis of PD. 3.350 STUDIES ON THE PROTECTIVE ROLE OF URIC ACID IN 6-HYDROXYDOPAMINE-INDUCED INJURY OF PC12 CELLS 1
2
1
2
W. Luo , X. Wang . The Department of Neurology, The Department of Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China Objective: To investigate the protective role of uric acid (UA) in the oxidative injury of 6-hydroxydopamine (6-OHDA) on PC12 cells. Methods: The highly differentiated PC12 cells were divided into 4 groups: the control, 6-OHDA, UA and 6-OHDA plus UA. Each of group was subdivided into a further 3 subgroups and cultured
S231
in vitro for 6, 12 and 24 hours respectively. The content of Lactate dehydrogenas (LDH), 8-hydroxy 2’-deoxyguanosine (8OHdG), superoxide dismutase (SOD) in the culture medium and intracellular malondialdehyde (MDA), glutathione (GSH) were detected. Results: The release of LDH and contents of MDA and 8-OHdG in the group treated with 100 mmol·L−1 6-OHDA for 12 and 24 h were significantly increased compared with the control group, while the release of LDH and contents of MDA and 8-OHdG were decreased, which were reversed by 200 mmol/L UA treatment (P < 0.05). The activity of SOD and GSH in cells treated with 100 mmol·L−1 6-OHDA for 12 and 24 h were significantly decreased, which were reversed by 200 mmol·L−1 UA treatment (P < 0.05). Conclusion: These results suggest that UA treatment can prevent PC12 cell from oxidative stress-mediated injury, which may associated with the increased activity of SOD and GSH. 3.351 THE EFFECTS OF INTRANIGRAL INJECTION OF GHRELIN ON HALOPERIDOL-INDUCED CATALEPSY IN RATS L. Shi, H. Jiang, J. Xie. Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Physiology, Medical College of Qingdao University, Qingdao, China Objective: Ghrelin, a natural ligand for the growth hormone secretagogue receptor 1a (GHS-R1a), is mainly secreted from stomach with small amounts produced in the brain. The expression of GHS-R1a in the dopaminergic neurons of substantia nigra (SN) indicates that SN might be a target site of ghrelin. We previously reported that ghrelin could protect dopaminergic neurons through GHS-R1a against neurotoxicity by inhibiting apoptosis, attenuating oxidative stress and enhancing the cell excitability. However, the role of ghrelin in motor coordination is largely unknown. Aim: The present study aims to explore the effects of intranigral injection of ghrelin on haloperidol-induced catalepsy in rats and analyze the dopamine activities in the striatum. Methods: Cannula-embedding technique, intranigral injection, behavior test, High-performance liquid chromatography electrochemical detection (HPLC-ECD) and Fast cyclic voltammetry (FCV) were used. Results: 1. Unilateral microinjection of ghrelin (1000 nmol/L) into the SN induced a contralateral dystonic posturing and attenuate the descent latency in the haloperidol-induced catalepsy rats. 2. Intracerebroventricular injection of ghrelin (1000 nmol/L) increased the dopamine turnover rate and dopamine release electrical stimulated by medial forebrain bundle in the striatum. Conclusion: Ghrelin is capable of attenuating haloperidol-induced catalepsy and regulating the motor function of SN. 3.352 EFFECTS OF GREEN TEA EXTRACT (GTE) ON HALOPERIDOL (HAL) INDUCED NEUROLEPTIC ANXIETY SYNDROME (NAS) AND PARKINSONISM IN RATS T. Malik, D.J. Haleem. Neurochemistry & Biochemical Neuropharmacology Unit, Biochemistry Department, The University of Karachi, Karachi, Pakistan Introduction: HAL elicits NAS along Parkinsonism. HAL induces c-Fos responsiveness in a distributed anxiety-related neural scheme, selected neuronal population of nucleus accumbens. Mood deficits by HAL metabolically effect via diet restriction that reduced body weight. GTE is known to control appetite and body weight while exerting anxiolytic effects. Aim: The current study testifies the hypothesis that GTE may control HAL elicited NAS with reducing Parkinsonism. Methods: Rats (n = 6) were treated with one of the four treatments; oral fluid [water/GTE (1 gm/liter)] plus saline; or oral fluid plus