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Gabaergic mechanisms of respiratory rhythm disturbances
PRESERVED INDUCTION OF LONG-TERM POTENTlATION IN THE STRATUM RADIATUM IN CA1 FIELD OF HIPPOCAMF’AL SLICES FROM TRANSGENIC MICE OVEREXPRESSING ORNITHINE DECARBOXYLASE AND OVERPRODUCING PUTRESCINE R. Pussinen’, J. SirviG’, L. Alhonen’, J. Larson’, M. HalmekytG’, E. Koivistoj and J. Jlnne’ A. I. Virtanen Institute’, Department of Neuroscience and Neurology’, Universiry of Kuopio, P. 0. Box 1627, FIN-70211 Kuopio, Finland, Centerfor the Neurobiology of Learning and Memory, Universiv of California, Irvine, CA 926972
TISSUE RESPONSE TO CELL DEGENERATION PROCESSES IN PATHOGENESIS OF CREUTZFELD - JAKOB DISEASE M.Nadrljanski School of Medicine, Universiq of Belgrade, Yugoslavia Cell degeneration processes in Creutzfeldt - Jakob Disease (CJD), causing the vacuolization of the neurons, apoptosis and causing astrogliosys, provoke the microglial response by expression of I32 integrins, TNF alpha and IL1. The cytokines are secreted in response to neurodegeneration, by microglial cells and by astrocytes. The same microglial cells, stimulated by the PrP fragment destroy the neurons by oxidative disorders and by production of neurotoxic agents. Endogenous peptides, the lipocortins with antiinflammatory action, especially against the cytokines are also secreted. According to electrophoretic research, the same protein spots, as those occuring only in herpes encephalitis are found. In CSF analyses, abnormally high levels of the specific 14-3-3 protein are found. The above mentioned evidence should support the hypothesis that the modificated local inflammatory-like response to cell degeneration, takes place during the pathogenesis of CJD.
The role of putrescine in synaptic neurotransmission and plasticity was studied using transgenic mice overexpressing omithine decarboxylase (ODC), a polyamine-synthesizing enzyme. Transgenic mice were produced using the standard microinjection technique leading to elevated levels of putrescine in the periphery and in the brain. The experiments investigated whether or not ODC mice with elevated levels of putrescine show alterations in synaptic transmission and induction of long-term potentiation in the CA1 field of the hippocampus in vitro. Our results indicated that (i) putrescine levels in brain slices of the transgenic mice were more than ten times higher than those in fresh slices of control mice although the absolute levels of putrescine and spermine decreased (by 15and 40 %, respectively) after 3-6 hr incubation in vitro while the levels of spermidine slightly increased (by 10 %), (ii) the excitatory synaptic response waveforms were wider (an increased halfwidth), and paired-pulse facilitation was somewhat reduced in ODC mice as compared to controls, and (iii) potentiation of excitatory synaptic responses (measured 30 - 45 minutes after theta burst stimulation) did not differ between ODC and control mice. These results indicate that synaptic transmission is affected, but synaptic plasticity in the field CA1 assessed in vitro is not changed by elevated levels of intracellular putrescine. GABAERGIC MECHANISMS OF RESPIRATORY RHYTHM DISTURBANCES V. A. Safonov, I. A. Tarakanov and L. N.Tikhomirova Institute of General Pathology and PathophysiologV of Russian Academia of Medical Sciences, Moscow, Russia
SOME CHANGES IN ANIMAL BEHAVIOUR WITH EXPERIMENTAL HEPATIC ENCEPHALOPATHY B. Petrovic, S. Zunic, S. Minic, N. Tacevic, D. Djordjevic Institute of Pathologic Physioloa, Faculty of Medicine, I 1000 Belgrade, Dr Subotica 9, Yugoslavia
One of the most prominent consequences of ischemic (hypoxic) damage in brain tissue is manifold increasing the GABA level in extracellular and cerebrospinal fluid. It was suggested that the excess of this inhibitory neurotransmitter carried with flow of cerebrospinal fluid and contacting to the bottom of IV ventricle can nonspecifically influence respiratory neurones of neighbouring dorsal respiratory group. In experiments on anaesthetised cats and rats (sodium pentobarbital, 40 mg/kg i.p.> it was established that GABA-positive substances such as sodium gamma-hydroxybutyrate, baclofen and GABA itself (systemic administrations and microinjections into dorsal respiratory group) enable the appearance of inspiratory neurone periodicity, blockade the pulmonary mechanoceptor afferentation and loss of respiratory chemosensitivity to carbon dioxide with preservation of respiratory chemosensitivity to oxygen. It is supposed that these respiratory alterations may comprise the basis for rhythm disturbances and respiratory subsequent appearance of pathological breathing such as apneuistic and periodic ones. It may explain why forebrain damages of different genesis can result in pathological breathing.
In male Wistar rats with experimental encephalopathy caused by liver disorders induced by thioacetamide we studied the performance of the test that required coordinated motor control. The performance of space delayed alternation test (DAT) was also subject of our study on the group of same experimental Wistar rats. In animals with induced encephalopathy a temporary dissary of motor function seeking coordinated motor control has occurred. The crossing bar time was prolonged significantly. Performance of previously learned DAT was changed and performing was decreased below the criterion level. Wilcoxon test confirmed high statistical significance in number ‘of errors before and after application of thioacetamide by which encephalopathy was induced. This finding of disability in performance of learned DAT was in agreement with Friedman test analysis. By this ANOVA analogue test high statistical significance was found between the number of errors at criterion and in animals with developed hepatic encephalopathy. Changes in behaviour were accompanied with some biochemical changes expressed in pathological profile of izoencymes in relevant parts of brain (prefrontal cortex. hippocampus, nucleus caudatus).
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TISSUE RESPONSE TO CELL DEGENERATION PROCESSES IN PATHOGENESIS OF CREUTZFELD - JAKOB DISEASE M.Nadrljanski School of Medicine, Universiq of Belgrade, Yugoslavia Cell degeneration processes in Creutzfeldt - Jakob Disease (CJD), causing the vacuolization of the neurons, apoptosis and causing astrogliosys, provoke the microglial response by expression of I32 integrins, TNF alpha and IL1. The cytokines are secreted in response to neurodegeneration, by microglial cells and by astrocytes. The same microglial cells, stimulated by the PrP fragment destroy the neurons by oxidative disorders and by production of neurotoxic agents. Endogenous peptides, the lipocortins with antiinflammatory action, especially against the cytokines are also secreted. According to electrophoretic research, the same protein spots, as those occuring only in herpes encephalitis are found. In CSF analyses, abnormally high levels of the specific 14-3-3 protein are found. The above mentioned evidence should support the hypothesis that the modificated local inflammatory-like response to cell degeneration, takes place during the pathogenesis of CJD.
The role of putrescine in synaptic neurotransmission and plasticity was studied using transgenic mice overexpressing omithine decarboxylase (ODC), a polyamine-synthesizing enzyme. Transgenic mice were produced using the standard microinjection technique leading to elevated levels of putrescine in the periphery and in the brain. The experiments investigated whether or not ODC mice with elevated levels of putrescine show alterations in synaptic transmission and induction of long-term potentiation in the CA1 field of the hippocampus in vitro. Our results indicated that (i) putrescine levels in brain slices of the transgenic mice were more than ten times higher than those in fresh slices of control mice although the absolute levels of putrescine and spermine decreased (by 15and 40 %, respectively) after 3-6 hr incubation in vitro while the levels of spermidine slightly increased (by 10 %), (ii) the excitatory synaptic response waveforms were wider (an increased halfwidth), and paired-pulse facilitation was somewhat reduced in ODC mice as compared to controls, and (iii) potentiation of excitatory synaptic responses (measured 30 - 45 minutes after theta burst stimulation) did not differ between ODC and control mice. These results indicate that synaptic transmission is affected, but synaptic plasticity in the field CA1 assessed in vitro is not changed by elevated levels of intracellular putrescine. GABAERGIC MECHANISMS OF RESPIRATORY RHYTHM DISTURBANCES V. A. Safonov, I. A. Tarakanov and L. N.Tikhomirova Institute of General Pathology and PathophysiologV of Russian Academia of Medical Sciences, Moscow, Russia
SOME CHANGES IN ANIMAL BEHAVIOUR WITH EXPERIMENTAL HEPATIC ENCEPHALOPATHY B. Petrovic, S. Zunic, S. Minic, N. Tacevic, D. Djordjevic Institute of Pathologic Physioloa, Faculty of Medicine, I 1000 Belgrade, Dr Subotica 9, Yugoslavia
One of the most prominent consequences of ischemic (hypoxic) damage in brain tissue is manifold increasing the GABA level in extracellular and cerebrospinal fluid. It was suggested that the excess of this inhibitory neurotransmitter carried with flow of cerebrospinal fluid and contacting to the bottom of IV ventricle can nonspecifically influence respiratory neurones of neighbouring dorsal respiratory group. In experiments on anaesthetised cats and rats (sodium pentobarbital, 40 mg/kg i.p.> it was established that GABA-positive substances such as sodium gamma-hydroxybutyrate, baclofen and GABA itself (systemic administrations and microinjections into dorsal respiratory group) enable the appearance of inspiratory neurone periodicity, blockade the pulmonary mechanoceptor afferentation and loss of respiratory chemosensitivity to carbon dioxide with preservation of respiratory chemosensitivity to oxygen. It is supposed that these respiratory alterations may comprise the basis for rhythm disturbances and respiratory subsequent appearance of pathological breathing such as apneuistic and periodic ones. It may explain why forebrain damages of different genesis can result in pathological breathing.
In male Wistar rats with experimental encephalopathy caused by liver disorders induced by thioacetamide we studied the performance of the test that required coordinated motor control. The performance of space delayed alternation test (DAT) was also subject of our study on the group of same experimental Wistar rats. In animals with induced encephalopathy a temporary dissary of motor function seeking coordinated motor control has occurred. The crossing bar time was prolonged significantly. Performance of previously learned DAT was changed and performing was decreased below the criterion level. Wilcoxon test confirmed high statistical significance in number ‘of errors before and after application of thioacetamide by which encephalopathy was induced. This finding of disability in performance of learned DAT was in agreement with Friedman test analysis. By this ANOVA analogue test high statistical significance was found between the number of errors at criterion and in animals with developed hepatic encephalopathy. Changes in behaviour were accompanied with some biochemical changes expressed in pathological profile of izoencymes in relevant parts of brain (prefrontal cortex. hippocampus, nucleus caudatus).
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