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P.5.e.001 The role of glutamate dehydrogenase activity in neuroexcitotoxic glutamate developement
P.5.e Dementia and neurological disorders – Other (clinical) with IC50 ≈ 10±15mM and IC50 ≈ 20±25mM. We have shown also that alfa-allomargaritarine and beta increase the threshold of calcium-induced swelling and depolarization of mitochondria. This effect is accompanied with the increasing of calcium retention capacity of mitochondria and not connected with impairment of respiratory function of mitochondria. Also these compounds prevent the Fe3+-induced lipid peroxidation in rat brain homogenates. References [1] Bachurin SO, Shevtsova EP, Kireeva EG, Oxenkrug GF, Sablin SO, 2003, Mitochondria as a target for neurotoxins and neuroprotective agents. Ann NY Acad Sci 993: 334–344. [2] Lin X, Jun-Tian Z, 2004, Neuroprotection by D-securinine against neurotoxicity induced by beta-amyloid (25−35). Neurol Res 26(7): 792−6.
P.5.e Dementia and neurological disorders – Other (clinical) P.5.e.001 The role of glutamate dehydrogenase activity in neuroexcitotoxic glutamate developement M. Kravos1 ° , I. Malesic2 . 1 Psychiatric private practice, Outpatient department, Slovenska Bistrica, Slovenia; 2 Institute for clinical biochemistry, Medical faculty University of Maribor, Maribor, Slovenia Purpose of the study: Glutamate is present in central nervous system in high concentrations and is the most important excitatory neurotransmitter. Glutamate dehydrogenase (GLDH) is intracellular enzyme normally located in mitochondria, mainly in tissues rich with mitochondrial matrix, and in rough endoplasmic reticulum of all cells, except in erythrocytes. Gene for GLDH1 (housekeeping), mostly to be found in hepatocytes, is located on chromosome 10 and gene for GLDH2 (nerve tissue specific) most is found in brain, retina, testis and leukocytes, on chromosome X [1]. In brain worn-out neuron branches are eliminated from dendrites to enable new sprouts by a normal excitotoxic mechanism. Excitotoxic mechanism is thought to be caused by patological process triggered by excessive glutamate activity [2]. Metabolism of neuroexcitotoxic glutamate is altered in certain forms of neurological and psychiatric diseases (olivopontocerebellar atrophy, bulbar palsy, motor neural degeneration, cerebellar ataxia, atypical Parkinson’s and Alzheimer’s diseases). We do not know any relevant data about the effect of GLDH in leukocytes so far. In patients, with GLDH deficiency in leukocytes, were discovered extrapyramidal signs and disfunctions in cerebellar domain. These patients have lower GLDH1 activity (up to 40%) in leukocytes and astrocytic processes, what may cause defective metabolism of transmitter glutamate at nerve terminals, leading to accumulation of glutamate and degeneration of postsynaptic neurons. Presumably, it is a systemic-metabolic damage, but displayed as brain disease because of high glutamate concentrations in the brain [1,3]. Methods: Defining GLDH activity in leukocytes can give us indirect data about neurodegenerative processes in brain, thus we developed our own method. Leukocytes isolation from venous blood was performed by Skoog and Beck method but cells disruption was caused within two freeze-thaw cycles and addition of TritonX-100 in the second cycle at −20o C
S515
Results: GLDH activity has been researched on leukocytes of 115 healthy subjects – 29 (25.2%) female and 86 (74.8%) male – aged from 20 to 65 years. The mean catalytic activity was by 24.67% higher in men (0.86 mkat/g) than in women (0.69 mkat/g), highest values were discovered in under 30-year-old patients by 0.75 mkat/g in men and 1.01 mkat/g in women. GLDH activity decreases slower in the age-group 30 to 50, yet evidently more rapidly afterwards, particularly in men where activity drops to 0.33 mkat/g, whereas in women to 0.45 mkat/g. The interval of 5- and 95-percentiles was chosen for the reference values. The interval from 0.12 – 1.24 mkat/g in men and 0.09 – 1.14 mkat/g in women were calculated in this manner. Conclusions: We have detected the highest GLDH values in healthy subjects younger than 30 years, both male as well as female. Mean values in men are higher than in women. GLDH activity in leukocytes diminishes with ageing in both groups, particularly after the age of 50. It is assumed that the same process takes place also in the brain. It is possible to conclude that lower GLDH activity in leukocytes and brain may be one of key factors for neurodegenerative ageing processes. References [1] Plaitakis A, Spanaki C, Mastorodemos V, Zaganas I. Study of structurefunction relationships in human glutamate dehydrogenases reveals novel molecular mechanisms for the regulation of the nerve tissuespecific (GLUD2) isoenzyme. Neurochem Int 2003; 43: 401–410. [2] Shashidharan P, Michealidis TM, Robakis NK, Kresovali A, Papamatheakis J, Plaitakis A. Novel human glutamate dehydrogenase expressed in neural and testicular tissues and encoded by an X-linked intronless gene. J Biol Chem 1994; 24: 16971–16976. [3] Iwatsuji K, Nakamura S, Kameyama M. Lymphocite glutamate dehydrogenase activity in normal aging and neurological diseases. Gerontology 1989; 35: 218 – 224.
P.5.e.002 Regional cerebral blood flow in patients with alcohol related dementia: a SPECT study H.J. Go1 ° , Y. Chung1 , S. Choi2 , K. Joe3 , Y. Cheon4 , D. Kim5 . 1 The cathoic university of Korea, Radiology, Seoul, SouthKorea; 2 University of Ulsan college of medicine, Psychiatry, Ulsan, South-Korea; 3 Incheon Chamsarang hospital, Psychiatry, Incheon, South-Korea; 4 Eulji university, Social welfare with addiction rehabilitation, Sungnam, South-Korea; 5 The caltholic university of Korea, Psychiatry, Seoul, South-Korea Purpose: There have been neuroimaging studies that focused on regional cerebral blood flow (rCBF) changes in chronic alcoholic patients, and their main common findings were frontal hypoperfusion. Studies have shown that the long-term use of alcohol decreases the metabolic rates and rCBF changes but there has been no study that directly focuses on the dementia resulted from alcohol consumption. The purpose of this study was to investigate rCBF changes using 1110 MBq of Tc-99m ECD SPECT in alcohol related dementia (ARD) patients. Methods: Twenty-five patients were included; all of whom with ARD, as diagnosed by the criteria that was outlined by Oslin, and twenty two healthy male volunteers were included as the control group. The general cognitive state was determined by a Korean version of the Mini Mental State Examination and the Clinical Dementia Rating Scale along with the Global Deterioration Scale in order to evaluate the severity of dementia. SPECT images were obtained 40 minutes after intravenous injection of 1110 MBq of Tc-99m ECD using a dual-head gamma camera (ECAM plus; Siemens, Erlangen, Germany) equipped with a low-energy,
P.5.e Dementia and neurological disorders – Other (clinical) P.5.e.001 The role of glutamate dehydrogenase activity in neuroexcitotoxic glutamate developement M. Kravos1 ° , I. Malesic2 . 1 Psychiatric private practice, Outpatient department, Slovenska Bistrica, Slovenia; 2 Institute for clinical biochemistry, Medical faculty University of Maribor, Maribor, Slovenia Purpose of the study: Glutamate is present in central nervous system in high concentrations and is the most important excitatory neurotransmitter. Glutamate dehydrogenase (GLDH) is intracellular enzyme normally located in mitochondria, mainly in tissues rich with mitochondrial matrix, and in rough endoplasmic reticulum of all cells, except in erythrocytes. Gene for GLDH1 (housekeeping), mostly to be found in hepatocytes, is located on chromosome 10 and gene for GLDH2 (nerve tissue specific) most is found in brain, retina, testis and leukocytes, on chromosome X [1]. In brain worn-out neuron branches are eliminated from dendrites to enable new sprouts by a normal excitotoxic mechanism. Excitotoxic mechanism is thought to be caused by patological process triggered by excessive glutamate activity [2]. Metabolism of neuroexcitotoxic glutamate is altered in certain forms of neurological and psychiatric diseases (olivopontocerebellar atrophy, bulbar palsy, motor neural degeneration, cerebellar ataxia, atypical Parkinson’s and Alzheimer’s diseases). We do not know any relevant data about the effect of GLDH in leukocytes so far. In patients, with GLDH deficiency in leukocytes, were discovered extrapyramidal signs and disfunctions in cerebellar domain. These patients have lower GLDH1 activity (up to 40%) in leukocytes and astrocytic processes, what may cause defective metabolism of transmitter glutamate at nerve terminals, leading to accumulation of glutamate and degeneration of postsynaptic neurons. Presumably, it is a systemic-metabolic damage, but displayed as brain disease because of high glutamate concentrations in the brain [1,3]. Methods: Defining GLDH activity in leukocytes can give us indirect data about neurodegenerative processes in brain, thus we developed our own method. Leukocytes isolation from venous blood was performed by Skoog and Beck method but cells disruption was caused within two freeze-thaw cycles and addition of TritonX-100 in the second cycle at −20o C
S515
Results: GLDH activity has been researched on leukocytes of 115 healthy subjects – 29 (25.2%) female and 86 (74.8%) male – aged from 20 to 65 years. The mean catalytic activity was by 24.67% higher in men (0.86 mkat/g) than in women (0.69 mkat/g), highest values were discovered in under 30-year-old patients by 0.75 mkat/g in men and 1.01 mkat/g in women. GLDH activity decreases slower in the age-group 30 to 50, yet evidently more rapidly afterwards, particularly in men where activity drops to 0.33 mkat/g, whereas in women to 0.45 mkat/g. The interval of 5- and 95-percentiles was chosen for the reference values. The interval from 0.12 – 1.24 mkat/g in men and 0.09 – 1.14 mkat/g in women were calculated in this manner. Conclusions: We have detected the highest GLDH values in healthy subjects younger than 30 years, both male as well as female. Mean values in men are higher than in women. GLDH activity in leukocytes diminishes with ageing in both groups, particularly after the age of 50. It is assumed that the same process takes place also in the brain. It is possible to conclude that lower GLDH activity in leukocytes and brain may be one of key factors for neurodegenerative ageing processes. References [1] Plaitakis A, Spanaki C, Mastorodemos V, Zaganas I. Study of structurefunction relationships in human glutamate dehydrogenases reveals novel molecular mechanisms for the regulation of the nerve tissuespecific (GLUD2) isoenzyme. Neurochem Int 2003; 43: 401–410. [2] Shashidharan P, Michealidis TM, Robakis NK, Kresovali A, Papamatheakis J, Plaitakis A. Novel human glutamate dehydrogenase expressed in neural and testicular tissues and encoded by an X-linked intronless gene. J Biol Chem 1994; 24: 16971–16976. [3] Iwatsuji K, Nakamura S, Kameyama M. Lymphocite glutamate dehydrogenase activity in normal aging and neurological diseases. Gerontology 1989; 35: 218 – 224.
P.5.e.002 Regional cerebral blood flow in patients with alcohol related dementia: a SPECT study H.J. Go1 ° , Y. Chung1 , S. Choi2 , K. Joe3 , Y. Cheon4 , D. Kim5 . 1 The cathoic university of Korea, Radiology, Seoul, SouthKorea; 2 University of Ulsan college of medicine, Psychiatry, Ulsan, South-Korea; 3 Incheon Chamsarang hospital, Psychiatry, Incheon, South-Korea; 4 Eulji university, Social welfare with addiction rehabilitation, Sungnam, South-Korea; 5 The caltholic university of Korea, Psychiatry, Seoul, South-Korea Purpose: There have been neuroimaging studies that focused on regional cerebral blood flow (rCBF) changes in chronic alcoholic patients, and their main common findings were frontal hypoperfusion. Studies have shown that the long-term use of alcohol decreases the metabolic rates and rCBF changes but there has been no study that directly focuses on the dementia resulted from alcohol consumption. The purpose of this study was to investigate rCBF changes using 1110 MBq of Tc-99m ECD SPECT in alcohol related dementia (ARD) patients. Methods: Twenty-five patients were included; all of whom with ARD, as diagnosed by the criteria that was outlined by Oslin, and twenty two healthy male volunteers were included as the control group. The general cognitive state was determined by a Korean version of the Mini Mental State Examination and the Clinical Dementia Rating Scale along with the Global Deterioration Scale in order to evaluate the severity of dementia. SPECT images were obtained 40 minutes after intravenous injection of 1110 MBq of Tc-99m ECD using a dual-head gamma camera (ECAM plus; Siemens, Erlangen, Germany) equipped with a low-energy,