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  • Electronic Resource  (11)
  • 2000-2004  (4)
  • 1975-1979  (7)
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  • Electronic Resource  (11)
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  • 1
    Electronic Resource
    Electronic Resource
    Nitric oxide regulates cGMP-dependent cAMP-responsive element binding protein phosphorylation and Bcl-2 expression in cerebellar neurons: implication for a survival role of nitric oxide (2002)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 82 (2002), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Nitric oxide (NO) is a small, diffusible, highly reactive molecule with a dichotomous regulatory role in the brain: an intra- and intercellular messenger under physiological conditions and a neurodegenerative agent under pathological conditions. We have recently demonstrated that long-lasting exposure to an neuronal nitric oxide synthase (nNOS) inhibitor down-regulated serine/threonine kinase (Akt) survival pathway and caused apoptosis in cerebellar granule cell cultures. The present study further substantiates the role of NO in neuronal survival by demonstrating that blocking its production down-regulates the activity of cAMP-responsive element binding protein (CREB), a transcription factor involved in cell survival and synaptic plasticity. Pharmacological dissection of the pathway linking NO to CREB shows that cGMP and its kinase are intermediate effectors. We also identify Bcl-2 as one of the anti-apoptotic genes down-regulated by NO shortage and decreased CREB phosphorylation. These results not only confirm the role of CREB in neuronal survival but also provide circumstantial evidence for a novel link among NO, CREB activation and survival.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2002.01080.x
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  • 2
    Electronic Resource
    Electronic Resource
    Blockade of the NMDA receptor increases developmental apoptotic elimination of granule neurons and activates caspases in the rat cerebellum (2000)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 12 (2000), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Elimination of neurons produced in excess naturally occurs during brain development through programmed cell death. Among the many survival factors affecting this process, a role for neurotransmitters acting on specific receptors has been suggested. We have performed an in vivo pharmacological blockade of the N-methyl- d-aspartate (NMDA) subtype of glutamate receptors, using the competitive NMDA receptor antagonist CGP 39551 at developmental stages corresponding to those at which a survival dependence on the stimulation of this receptor has been demonstrated for cerebellar granule neurons explanted in culture (typically from postnatal day 7 to postnatal day 11 or 13). We were able to demonstrate an increased level of DNA fragmentation in the cerebellum of the treated rats. At the P11 stage, in particular, the fragmented DNA extracted from the cerebellum of CGP 39551-treated pups showed a clear laddering of nucleosomal fragments after agarose-gel electrophoresis. Accordingly, in situ TUNEL technique showed a remarkable increase of cells positive for nucleosomal DNA fragmentation, particularly in the inner granular layer of the cerebellum of treated rats at P11 stage. Therefore, the natural rate of apoptotic elimination of cerebellar granule neurons is considerably enhanced under conditions of pharmacological blockade of the NMDA receptor, thus demonstrating, for the first time in vivo, a clear survival dependence of these neurons upon the stimulation of the NMDA receptor. Concomitantly with the increased rate of apoptotic elimination of granule neurons, the activity of two death proteases of the caspase family, in particular of caspase 3 and caspase 1 at a lower extent, was remarkably increased in the cerebellum of the treated rats. On the contrary, a marker related to the normal differentiation process of granule neurons, the enzyme ornithine decarboxylase, was strongly decreased in its activity in the cerebellum of treated rat pups.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2000.00189.x
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  • 3
    Electronic Resource
    Electronic Resource
    NMDA receptor-dependent CREB activation in survival of cerebellar granule cells during in vivo and in vitro development (2002)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 16 (2002), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: During both in vivo and in vitro development, cerebellar granule cells depend on the activity of the NMDA glutamate receptor subtype for survival and full differentiation. With the present results, we demonstrate that CREB activation, downstream of the NMDA receptor, is a necessary step to ensure survival of these neurons. The levels of CREB expression and activity increase progressively during the second week of postnatal cerebellar development and the phosphorylated form of CREB is localized selectively to cerebellar granule cells during the critical developmental stages examined. Chronically blocking the NMDA receptor through systemic administration of the competitive antagonist, CGP 39551, during the in vivo critical developmental period, between 7–11 postnatal days, results in increased apoptotic elimination of differentiating granule neurons in the cerebellum [Monti & Contestabile, Eur. J. Neurosci., 12, 3117–3123 (2000)]. We report here that this event is accompanied by a significant decrease of CREB phosphorylation in the cerebellum of treated rat pups. When cerebellar granule neurons are explanted and maintained in dissociated cultures, the levels of CREB phosphorylation increase with differentiation, similar to that which happens during in vivo development. When granule cells are kept in non-trophic conditions, their viability is affected and both CREB phosphorylation and transcriptional activity are decreased significantly. The neuronal viability and the deficiency of CREB activity, are both rescued by the pharmacological activation of the NMDA receptor. These results provide good circumstantial evidence for a functional link between the NMDA receptor and CREB activity in promoting neuronal survival during development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2002.02232.x
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  • 4
    Electronic Resource
    Electronic Resource
    Akt pathway mediates a cGMP-dependent survival role of nitric oxide in cerebellar granule neurones (2002)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 81 (2002), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Apoptotic death results from disrupting the balance between anti-apoptotic and pro-apoptotic cellular signals. The inter- and intracellular messenger nitric oxide is known to mediate either death or survival of neurones. In the present work, cerebellar granule cells were used as a model to assess the survival role of nitric oxide and to find novel signal transduction pathways related to this role. It is reported that sustained inhibition of nitric oxide production induces apoptosis in differentiated cerebellar granule neurones and that compounds that slowly release nitric oxide significantly revert this effect. Neuronal death was also reverted by a caspase-3-like inhibitor and by a cyclic GMP analogue, thus suggesting that nitric oxide-induced activation of guanylate cyclase is essential for the survival of these neurones. We also report that the Akt/GSK-3 kinase system is a transduction pathway related to the survival action of nitric oxide, as apoptosis caused by nitric oxide deprivation is accompanied by down-regulation of this, but not of other, kinase systems. Conversely, treatments able to rescue neurones from apoptosis also counteracted this down-regulation. Furthermore, in transfection experiments, overexpression of the Akt gene significantly decreased nitric oxide deprivation-related apoptosis. These results are the first evidence for a mechanism where endogenous nitric oxide promotes neuronal survival via Akt/GSK-3 pathway.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2002.00857.x
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  • 5
    Electronic Resource
    Electronic Resource
    Ultrastructural pattern of acetylcholinesterase distribution in the cerebellar cortex of the quail (1977)
    Springer
    Anatomy and embryology 152 (1977), S. 29-41 
    Details
    ISSN: 1432-0568
    Keywords: Cerebellum ; Acetylcholinesterase ; Ultrastructural cytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructural localization of acetylcholinesterase (AChE) was studied in the cerebellar cortex of the quail by means of histochemical methods. The greater amount of AChE was detected at level of the molecular layer in the intercellular spaces between parallel fibers and between parallel fibers and dendritic terminals. Many neurons showed intracellular localization of enzyme activity: the AChE positive neurons were all Golgi cells, most stellate and basket cells and different aliquots of Purkinje and granule cells. The enzymatic activity was usually localized in the cisternae of endoplasmic reticulum, in the nuclear envelope (but this last localization was not present in Purkinje cells) and sometimes in the Golgi apparatus; reaction granules were usually scarce in the different dendritic branches ramifying in the molecular layer. On the basis of the ultrastructural pattern of AChE distribution, some considerations are developed on the methodological aspects concerning the reliability of histochemical methods, the differences recorded at light and electron microscope level, the problems related to extracellular localization of enzyme, the difficulty of establishing a precise correlation between AChE localization in a cerebellar neuron and its possible cholinergic and/or cholonoceptive nature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00341433
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  • 6
    Electronic Resource
    Electronic Resource
    Ultrastructural analysis on acetylcholinesterase localization in the cerebellar cortex of teleosts (1977)
    Springer
    Anatomy and embryology 152 (1977), S. 15-27 
    Details
    ISSN: 1432-0568
    Keywords: Fish cerebellum ; Acetylcholinesterase ; Ultrastructural cytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The histochemical localization of acetylcholinesterase (AChE) was studied by electron microscopy in the cerebellar cortex of the goldfish and the catfish. The patterns of enzyme distribution show noticeable differences in the two teleost species at the level of the corresponding cerebellar structures. Among the most distinctive features in the prevailing intracellular localization of enzyme activity in the goldfish and the prevailing extracellular localization in the catfish in the molecular layer and, to a lesser extent, the granular layer. Only quantitative differences in the ability to synthesize AChE can be recorded among the different cerebellar neurons in the two species, since all these neurons exhibit different amounts of enzyme activity linked to their cytoplasmic structures. Comparing the results obtained with those of previous histochemical, experimental and developmental researches, the hypothesis seems well founded that the embryonic pool of cerebellar neurons is made up to AChE-synthesizing neuroblasts which, during development, lose or maintain to a different degree the mechanisms for AChE synthesis. In addition the light and electron microscope histochemistry reveals at different levels of resolution that the final pattern of AChE distribution in the cerebellar cortex is the sum of different degrees of AChE synthesis by cerebellar neurons and different degrees of enzyme release in extracellular spaces.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00341432
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  • 7
    Electronic Resource
    Electronic Resource
    Methodological aspects of the histochemical localization and activity of some cerebellar dehydrogenases (1978)
    Springer
    Histochemistry and cell biology 56 (1978), S. 117-132 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In a detailed study focused on the methodological problems in dehydrogenase histochemistry [e.g., fixation, diffusion of enzymes and of reduced inermediates, conversion of NADPH and NADP to NADH and NAD, respectively, penetration of tetrazolium salt and formazan substantivity, ‘nothing dehydrogenase’ reaction, use of exogenous CoQ10 and of flavoprotein substitute (PMS)], the distribution and activity of succinate dehydrogenase, NAD(P)H-tetrazolium reductase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase (H and M types), and of l-glutamate dehydrogenase (E.C. 1.4.1.2 and E.C. 1.4.1.3) have been investigated in the rat cerebellum. It was evident from the study that reliable results could only be obtained if all the aforementioned factors had been considered. The image of actual concentration of SDH in the neuropil of the molecular layer could only be recorded by adding CoQ10, while other structures exhibited greater balance between SDH and endogenous mitochondrial CoQ. Contrary to previous studies, a reversed localization of the activity of G-6-PDH and LDH was noticed. The elements of molecular and Purkinje layers were rich in G-6-PDH, while the granular layer was nearly depleted. The actual level of LDH could only be recorded if NADH-tetrazolium reductase was bypassed with PMS. The H and M types of LDH coexisted in the three cortical layers, the H type being prevalent and the M type attaining its highest level in synaptic glomeruli followed by the structures of the molecular layer and the Purkinje cells. High activity of GDH was noticed in Bergmann glia followed by synaptic glomeruli, while most other structures showed weak to moderate activity. The two GDH types coexisted in all structures showing activity, except for Bergmann cells, which only showed presence of the E.C. 1.4.1.3 type. Furthermore, Bergmann glia was exceptional by showing no activity of SDH and LDH, but strong activity of G-6-PDH and NADPH-tetrazolium reductase. The granular cells were exceptional by showing weak or no activity of all enzymes in question.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508438
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  • 8
    Electronic Resource
    Electronic Resource
    Cholinesterase patterns in the cerebellum of reptiles (1977)
    Springer
    Histochemistry and cell biology 51 (1977), S. 195-200 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In the cerebellum of four species belonging to the three main reptilian orders the histochemical localization of cholinesterases has been studied. The use of different substrate-inhibitor combinations permits to record the distribution patterns of acetylcholinesterase and pseudocholinesterase, mainly revealed as butyrylcholinesterase activity. From the neurological point of view it is interesting to note that acetylcholinesterase activity shows three different distribution patterns in reptilian cerebellum, thus confirming the characteristic variability previously noticed in the cerebellar cortex of other vertebrates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567223
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  • 9
    Electronic Resource
    Electronic Resource
    The pyridine nucleotide and non-pyridine nucleotide dependence of L-glutamate dehydrogenase in the histochemical system (1977)
    Springer
    Histochemistry and cell biology 53 (1977), S. 117-133 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Under histochemical conditions (fresh frozen sections from liver, kidney and cerebellum of the rat) it was shown that the oxidation of L-glutamic acid was carried out by the NAD-dependent L-glutamate dehydrogenase (E.C. 1.4.1.2) and/or the NAD- or NADP-dependent L-glutamate dehydrogenase (E.C. 1.4.1.3) as well as by an enzyme system which is not dependent on externally added NAD, NADP, FAD, FMN or CoQ10 for activity. This non-pyridine dependent activity was related to the L-glutamate dehydrogenases proper, owing to the following: a) the localization of activity noticed corresponds to that obtained with the NAD- or NADP-containing media, b) the incubation time needed for initial formation of red and blue formazans is similar to that with coenzyme-containing media, c) pre-extraction experiments reveal similarity in enzyme diffusion rates, d) the named activity is influenced by the same agents and to the same extent as the activity obtained by the inclusion of NAD or NADP (e.g. dissociation of the dehydrogenase molecule into subunits due to urea, inhibition of activity due to N-ethyl maleimide and 1.10-phenanthroline, activation due to the allosteric effect of ADP and to high substrate concentration, allosteric inhibition caused by GTP and inhibition caused by α-ketoglutaric acid, no inhibitory effect of KCN), and e) the named activity was not affected by added PMS (excluding activity due to L-aminoacid oxidase). In the in situ localization of enzyme activity it was found that L-glutamate dehydrogenases E.C. 1.4.1.2 and E.C. 1.4.1.3 co-exist in the cells of kidney and cerebellum, while the L-glutamate dehydrogenase E.C. 1.4.1.3 only was present in liver cells. Finally, it was stated that incubation time should be kept as short as possible in order to avoid “Nothing dehydrogenase” reaction as well as inhibition due to accumulation of α-ketoglutaric acid. Only “gel” incubation media should be applied.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00498487
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  • 10
    Electronic Resource
    Electronic Resource
    Histochemical localization of acetylcholinesterase in the cerebellum and optic tectum of four freshwater teleosts (1975)
    Springer
    Histochemistry and cell biology 45 (1975), S. 279-288 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A histochemical study has been carried out on the localization of acetylcholinesterase (AChE) in the cerebellum and optic tectum of four species of freshwater teleosts. AChE distribution in the cerebellar cortex of teleosts shows differences among the species examined and, in the trout, also differences between different cerebellar areas. This uneven kind of enzyme distribution corresponds to a similar variety of AChE patterns noticed in other vertebrates, especially mammals. AChE distribution in the optic tectum shows a prevalent pattern characterized by precise laminar distribution of enzymatic activity which is alternatively strong, weak or absent in the different tectal layers. The results suggest that most of sensitive imput and many systems of stimuli propagation may be mediated by cholinergic mechanisms in the optic tectum of teleosts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00492630
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