Molecular and chemical neuropathology最新文献

{"title":"Dual response of calpain to rat brain postdecapitative ischemia.","authors":"T Zalewska,&nbsp;B Zabłocka,&nbsp;T C Saido,&nbsp;H Zajac,&nbsp;K Domańska-Janik","doi":"10.1007/BF02815181","DOIUrl":"https://doi.org/10.1007/BF02815181","url":null,"abstract":"<p><p>Calpains, Ca(2+)-dependent neutral proteinases (microM and mM Ca(2+)-sensitive), and their endogenous inhibitor calpastatin were examined in rat brain. Specific activity of m-calpain exceeded almost 10 times that of mu-calpain, and the both isoforms of calpain together with calpastatin were mainly located in the soluble fraction of homogenate. Acute postdecapitative ischemia of 15 min duration resulted in a gradual, time-dependent decrease of total mu-calpain activity (to 60% of control values) and in the moderate elevation of calpastatin activity (by 28%). The decrease of total mu-calpain activity coincided with its remarkable increase (above 300% of control values) in particulate fraction. In the case of m-calpain, the only observed effect of ischemia was its redistribution and, as a consequence, the elevation of activity in particulate fraction. The accumulation of breakdown products, resulting from calpain-catalyzed proteolysis of fodrin (as revealed by Western blotting) indicated activation of calpain under ischemia. The findings suggest that this rapid activation involves partial enzyme translocation toward membranes, and is followed (at least in acute phase) by mu-calpain downregulation and increased calpastatin activity.</p>","PeriodicalId":18736,"journal":{"name":"Molecular and chemical neuropathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02815181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20561007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tyrosine hydroxylase mRNA levels in locus ceruleus of rats during adaptation to long-term immobilization stress exposure.","authors":"M Rusnák,&nbsp;S Zórad,&nbsp;P Buckendahl,&nbsp;E L Sabban,&nbsp;R Kvetnanský","doi":"10.1007/BF02815186","DOIUrl":"https://doi.org/10.1007/BF02815186","url":null,"abstract":"<p><p>The major central norepinephrinergic nucleus, locus ceruleus (LC), is thought to participate in modulation of such brain areas as cerebral cortex, septum, hippocampus, thalamus, hypothalamus, and cerebellum in animals facing various physiological challenges, including stress. Exposure of experimental animals to different stressors causes an increase in LC activity and gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. The aim of this work was to investigate the effect of a single and repeated (7 times) or long-term repeated (42 times) daily immobilization stress (IMMO) on TH mRNA levels in LC of laboratory rats by in situ hybridization method. A single IMMO caused significant elevation of LC TH mRNA levels in comparison to unstressed controls. This was found immediately and at 3 and 6 h after IMMO, and progressively increased up to 24 h after the first IMMO terminated. Further exposure to IMMO did not cause additional increases in LC TH mRNA levels, which stayed significantly elevated in comparison to unstressed rats. In animals that underwent IMMO for 42 times, the LC TH gene expression, 24 h after the last stress exposure, was significantly lower when compared to that of singly or seven times stressed rats. Thus, our results indicate a possible adaptation of catecholamine-synthesizing system at the level of TH gene expression in LC of rats exposed to long-term repeated IMMO.</p>","PeriodicalId":18736,"journal":{"name":"Molecular and chemical neuropathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02815186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20560924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution and isoform diversity of the organellar Ca2+ pumps in the brain.","authors":"F Baba-Aissa,&nbsp;L Raeymaekers,&nbsp;F Wuytack,&nbsp;L Dode,&nbsp;R Casteels","doi":"10.1007/BF02815182","DOIUrl":"https://doi.org/10.1007/BF02815182","url":null,"abstract":"<p><p>The gene family of organellar-type Ca2+ transport ATPases consists of three members. SERCA1 is expressed exclusively in fast skeletal muscle; SERCA2 is ubiquitously expressed, whereas SERCA3 is considered to be mainly expressed in cells of the hematopoietic lineage and in some epithelial cells. In the brain, the organellar-type Ca2+ transport ATPases are almost exclusively transcribed from the SERCA2 gene. Four different SERCA2 mRNAs have been described (classes 1-4). However, unlike in nonneuronal cells, which express the class 1, 2, and 3 splice variants, the main SERCA2 mRNA in the brain is the class 4 messenger. Similar to classes 2 and 3, the class 4 codes for the ubiquitously expressed SERCA2b protein. Recently, we have reported the distribution of the SERCA isoforms in the brain (Baba-Aissa et al., 1996a,b). SERCA2b was present in most neurons of all investigated brain regions. The highest levels were found in the Purkinje neurons of the cerebellum and in the pyramidal cells of the hippocampus. Interestingly, SERCA3 and SERCA2a are coexpressed along with SERCA2b in the Purkinje neurons, but are weakly expressed in the other brain regions if present at all. Since these three protein isoforms have a different affinity for Ca2+, their possible roles in relation to Ca2+ stores in neurons are discussed.</p>","PeriodicalId":18736,"journal":{"name":"Molecular and chemical neuropathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02815182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20561008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurochemical changes in the spinal cord in degenerative motor neuron diseases.","authors":"Y Nagata,&nbsp;K Fujita,&nbsp;M Yamauchi,&nbsp;T Kato,&nbsp;M Ando,&nbsp;M Honda","doi":"10.1007/BF02815185","DOIUrl":"https://doi.org/10.1007/BF02815185","url":null,"abstract":"<p><p>Human amyotrophic lateral sclerosis (ALS), a typical motor neuron disease, is characterized pathologically by selective degenerative loss of motoneurons in the CNS. We have demonstrated significant reductions of neurotransmitter-related factors, such as acetylcholine-(ACh)-synthesizing enzyme activity and glutamate and aspartate contents in the ALS, compared to the non-ALS spinal cord obtained at autopsy. We have also shown considerable reductions in activities of cytochrome-c oxidase (CO), an enzyme contributing to aerobic energy production, and transglutaminase (TG), a Ca(2+)-dependent marker enzyme for tissue degeneration, in the ALS spinal cord. We found marked increases in fragmented glial fibrillary acidic protein (GFAP), a filamentous protein specifically associated with reactive astrocytes, in the ALS spinal cord relative to non-ALS tissue. These biochemical results corresponded well to pathomor-phological neuronal degenerative loss and reactive proliferation of astroglial components in the ALS spinal cord tissue. However, these results only indicate the final pathological and biochemical outcomes of ALS, and it is difficult to follow up cause and process in the ALS spinal cord during progression of the disease. Therefore, we used an animal model closely resembling human ALS, motor neuron degeneration (Mnd) mutant mice, a subline of C57BL/6 that shows late-onset progressive degeneration of lower motor neurons with paralytic gait beginning around 6.5 mo of age, to follow the biochemical and pathological alterations during postnatal development. We detected significant decreases in CO activity during early development and in activity of superoxide dismutase (SOD), an antioxidant enzyme, in later stages in Mnd mutant spinal cord tissue. TG activity in the Mnd spinal cord showed gradual increases during early development reaching a maximum at 5 mo, and then tending to decrease thereafter. Amounts of fragmented GFAPs increased continuously during postnatal development in Mnd spinal cord. These biochemical changes were observed prior to the appearance of clinical motor dysfunctions in the Mnd mutant mice. Such biochemical analyses using appropriate animal models will be useful for inferring the origin and progression of human ALS.</p>","PeriodicalId":18736,"journal":{"name":"Molecular and chemical neuropathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02815185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20560923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of glutamate and inhibitors of NMDA receptors on postdenervation decrease of membrane potential in rat diaphragm.","authors":"A Kh Urazaev,&nbsp;N V Naumenko,&nbsp;G I Poletayev,&nbsp;E E Nikolsky,&nbsp;F Vyskocil","doi":"10.1007/BF02815179","DOIUrl":"https://doi.org/10.1007/BF02815179","url":null,"abstract":"<p><p>The early postdenervation depolarization of rat diaphragm muscle fibers (8-10 mV within 3 h in vitro) is substantially smaller (3 mV) when muscles are bathed with 1 x 10(-3) M L-glutamate (Glu) or 1 x 10(-3) M N-methyl-D-aspartate (NMDA). The effects of Glu and NMDA are inhibited in a dose-dependent manner by competitive inhibitor 2-amino-5-phosphonovaleric acid (APV) with Ki 6.3 x 10(-4) M, by 2 x 10(-7) M MK-801, which acts as an open channel inhibitor, by 2-3 x 10(-4) Zn2+, which reacts with surface-located sites of the NMDA subtype of the glutamate receptor, and also by glycine-free solutions and 7-Cl-kynurenic acid, which inhibits the glycine binding sites on NMDA receptors. It follows that the effect of glutamate on early post-denervation depolarization is mediated by the NMDA subtype of glutamate receptor with similar pharmacological properties to those found in neurons. The only exception found was the glutamate-like action of 1 x 10(-7) M MK-801, which partially prevented the early postdenervation depolarization when present in the muscle bath during the first 3 h after nerve section.</p>","PeriodicalId":18736,"journal":{"name":"Molecular and chemical neuropathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02815179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20561005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased expression of natriuretic peptide A receptors and decreased cGMP production in the choroid plexus of spontaneously hypertensive rats.","authors":"S Zorad,&nbsp;A Alsasua,&nbsp;J M Saavedra","doi":"10.1007/BF02815183","DOIUrl":"https://doi.org/10.1007/BF02815183","url":null,"abstract":"<p><p>Atrial natriuretic peptide receptor (ANP) subtypes and their signal transduction response were characterized in choroid plexus of spontaneously hypertensive (SHR) and normotensive (WKY) rats. We found two ANP receptor subtypes, guanylate cyclase coupled and uncoupled, in both rat strains. Binding of ANP was lower in SHR choroid plexus when compared to WKY. The lower ANP binding in SHR was the result of a decrease of binding to the guanylate cyclase-coupled receptor subtype A, a decrease that correlated well with the decreased ANP-induced cGMP formation in SHR. Forskolin stimulated cGMP production to the same extent in both strains. In WKY rats, ANP increased basal and forskolin-stimulated cAMP production; conversely, in SHR, ANP did not affect the basal level of cAMP and inhibited the forskolin-stimulated cAMP production. These results demonstrate differences in ANP receptor subtype expression, and ANP signal transduction in choroid plexus of hypertensive and normotensive rats, which is of possible significance to the central mechanisms of blood pressure control.</p>","PeriodicalId":18736,"journal":{"name":"Molecular and chemical neuropathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02815183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20561009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes of acetylcholinesterase activity in various parts of brain following nontreated and treated soman poisoning in rats.","authors":"J Kassa,&nbsp;J Bajgar","doi":"10.1007/BF02815180","DOIUrl":"https://doi.org/10.1007/BF02815180","url":null,"abstract":"<p><p>Changes of acetylcholinesterase (AChE) activity in various parts of the brain (frontal cortex, medulla oblongata, pons Varoli, cerebellum, hypothalamus, and hippocampus), following im sublethal non-treated and treated soman poisoning were studied. As a treatment, two antidotal mixtures containing atropine and either obidoxime or oxime HI-6 were used. This antidotal treatment was administered im for 30 s following soman intoxication. The AChE activities in the various brain tissues were evaluated at 1 and 3 h following soman administration. As expected, the highly toxic organophosphorus compound, soman, markedly inhibited AChE activity in all the brain sections at both time intervals. Both oximes had little influence on soman-induced AChE inhibition, but only the HI-6 mixture was able to reactivate soman-inhibited AChE significantly in some of the brain parts (frontal cortex, pons Varoli, hypothalamus). In the brain, the effect of HI-6 against soman-induced AChE inhibition is higher in comparison with obidoxime, but not quite satisfactory. Despite its limited effectiveness in the brain, HI-6 seems to be the most effective oxime yet found against soman poisoning because of its high reactivating effect in the peripheral compartment and other beneficial effects.</p>","PeriodicalId":18736,"journal":{"name":"Molecular and chemical neuropathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02815180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20561006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of hippocampal reoxygenation injury.","authors":"L Horáková,&nbsp;S Stolc,&nbsp;Z Chromíková,&nbsp;A Pekárová,&nbsp;L Derková","doi":"10.1007/BF02815184","DOIUrl":"https://doi.org/10.1007/BF02815184","url":null,"abstract":"<p><p>Mechanisms of 12 min of hypoxia and subsequent reoxygenation were studied in rat hippocampal slices. General cell injury in reoxygenation was indicated by increased lactate dehydrogenase (LDH). Increase in conjugated dienes (CD) showed that oxygen radical burst induced lipid peroxidation (LPO). ATP increase was also involved in reoxygenation injury, since cyanide, an inhibitor of ATP synthesis, decreased this damage. The results obtained on using inhibitors of oxygen radicals generation, i.e., allopurinol, indomethacin, rotenone, and antimycin A, strongly suggest that the sources of oxygen radicals were the xanthine/xanthine oxidase system, prostaglandin synthesis, and mitochondrial respiratory chain. The involvement of oxygen radicals in oxidative stress was confirmed also by using chain-breaking antioxidants, trolox alpha-tocopherol and stobadine, [(-)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido (4,3b)indole]. Stobadine added at the onset of reoxygenation was most effective, acting in a dose-dependent manner and found to be without effect when applied in hypoxia. Cytochrome-c oxidase was decreased in reoxygenated hippocampal slices treated with stobadine.</p>","PeriodicalId":18736,"journal":{"name":"Molecular and chemical neuropathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02815184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20561010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-DOPA exacerbates amphetamine-induced dopamine depletion.","authors":"C S Myers,&nbsp;M Witten,&nbsp;Y L Yu,&nbsp;G C Wagner","doi":"10.1007/BF02870183","DOIUrl":"https://doi.org/10.1007/BF02870183","url":null,"abstract":"<p><p>Administration of L-DOPA to Parkinson patients has been suggested to exacerbate \"functional denervation\" of the nigrostriatal system. Therefore, experiments were conducted to determine if L-DOPA combined with the DOPA decarboxylase inhibitor, Ro4-4602 (benserazide hydrochloride) would potentiate amphetamine-induced neurotoxicity. Mice received two injections of saline or benserazide + L-DOPA (25.0 or 100.0 mg/kg) interspersed with four injections of amphetamine (15.0 mg/kg) at 2-h intervals. Significant depletion of striatal dopamine, DOPAC, and HVA was evident 1 wk following amphetamine administered with or without 25.0 mg/kg L-DOPA + benserazide, whereas 100.0 mg/kg L-DOPA + benserazide potentiated amphetamine-induced depletion of striatal dopamine (17 vs 28% of control values). This enhanced toxicity may be consequent to increased dopamine turnover following L-DOPA (360 vs 231%), a situation akin to that observed in compromised dopaminergic nigrostriatal systems of parkinsonian patients. Furthermore, striatal 5-HT was not altered by amphetamine alone, whereas concurrent administration of L-DOPA/ benserazide depleted 5-HT to 82% of control values. No changes were evident in the frontal cortex following amphetamine with or without concurrent L-DOPA/benserazide; however, L-DOPA/benserazide administered alone reduced 5-HT and 5-HT turnover to 58% of control values.</p>","PeriodicalId":18736,"journal":{"name":"Molecular and chemical neuropathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02870183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20486493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anoxic injury of endothelial cells causes divergent changes in protein kinase C and protein kinase A signaling pathways.","authors":"P Grammas,&nbsp;P Moore,&nbsp;R E Cashman,&nbsp;R A Floyd","doi":"10.1007/BF02870185","DOIUrl":"https://doi.org/10.1007/BF02870185","url":null,"abstract":"<p><p>Alterations in protein kinase C (PKC) and cAMP-dependent kinase have been documented in anoxic brain injury. However, the regulation of these signaling enzymes in the cerebrovasculature has not been explored. In this study, cultured brain endothelial cells exposed to anoxic injury (anoxia--20 min/reoxygenation--40 min) showed both a significant increase (p < 0.001) in PKC and decrease (p < 0.01) in cAMP-dependent kinase activity. Analysis of PKC by Western blot indicated an increase in kinase level in response to anoxic injury, whereas there was no change in the level of cAMP-dependent protein kinase, as measured by labeled cAMP binding. Inhibition of nitric oxide synthase did not affect these changes. Addition of the nitric oxide-releasing compound sodium nitroprusside caused a dose-dependent increase in the activity of both signaling systems in endothelial cells. These data demonstrate that anoxic injury of brain endothelial cells in culture causes significant and divergent changes in signaling kinase activity. Abnormalities in brain endothelial PKC and cAMP-dependent kinase could have important consequences for the blood-brain barrier in anoxic brain injury.</p>","PeriodicalId":18736,"journal":{"name":"Molecular and chemical neuropathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02870185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20487078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}