Tachykinins and excitotoxicity in cerebellar granule cells
ABSTRACT The tachykinins represent an important group of neuropeptides that are widely distributed both in the central and peripheral nervous system where they perform several functions connected with neuronal modulation, often in synergy with glutamate excitatory transmission. While a great deal of data is available on their distribution and many studies have been performed by molecular, biochemical, and immunohistochemical techniques, much less is known about their physiological role, in particular in the cerebellum. This review is an attempt to summarize the diverse evidence suggesting a role for tachykinins in cerebellar granule neurons.
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- "The different structure of these proteins could be responsible for the selective modulation of Kv1.4 upregulation, without affecting Kv2.1 and Kv4.2 expression. In addition, the activity of Kv channels can be modulated indirectly via signal transduction pathways leading to modifications of Kv channel function and SP receptor activation involved different transduction pathways . "
ABSTRACT: Reduced levels of Substance P (SP), an endogenous neuropeptide endowed with neuroprotective and anti-apoptotic properties, have been found in brain and spinal fluid of Alzheimer's disease (AD) patients. Potassium (K+) channel dysfunction is implicated in AD development and the amyloid-β (Aβ)-induced up-regulation of voltage-gated potassium channel subunits could be considered a significant step in Aβ brain toxicity. The aim of this study was to evaluate whether SP could reduce, in vivo, Aβ-induced overexpression of Kv subunits. Rats were intracerebroventricularly infused with amyloid-β 25–35 (Aβ25–35, 20 µg) peptide. SP (50 µg/Kg, i.p.) was daily administered, for 7 days starting from the day of the surgery. Here we demonstrate that the Aβ infused rats showed impairment in cognitive performances in the Morris water maze task 4 weeks after Aβ25–35 infusion and that this impairing effect was prevented by SP administration. Kv1.4, Kv2.1 and Kv4.2 subunit levels were quantified in hippocampus and in cerebral cortex by Western blot analysis and immunofluorescence. Interestingly, SP reduced Kv1.4 levels overexpressed by Aβ, both in hippocampus and cerebral cortex. Our findings provide in vivo evidence for a neuroprotective activity of systemic administration of SP in a rat model of AD and suggest a possible mechanism underlying this effect.PLoS ONE 11/2013; 8(11):e78036. DOI:10.1371/journal.pone.0078036 · 3.23 Impact Factor
Conference Paper: Quality issues in database reverse engineering: an overview[Show abstract] [Hide abstract]
ABSTRACT: Database reverse engineering is the part of system maintenance work that produces a sufficient understanding of an existing database and its application domain to allow appropriate changes to be made. It is often difficult to obtain a good conceptual understanding of an old and ill-designed database, especially when there is a lack of documentation. Database reverse engineering attempts to provide solutions for these problems. Three quality issues regarding reverse engineering of existing databases are discussed: (1) the method of database design chosen to serve as the basis for reverse engineering, (2) thoroughness of domain semantics acquisition, and (3) performance evaluation criteria. These quality issues are important for any database reverse engineering method in order for it to perform at a high level of automation, and to obtain a conceptual schema that is semantically rich and correctEngineering Management Conference, 1995. 'Global Engineering Management: Emerging Trends in the Asia Pacific'., Proceedings of 1995 IEEE Annual International; 07/1995
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ABSTRACT: Research on the cerebellum is evolving rapidly. The exquisiteness of the cerebellar circuitry with a unique geometric arrangement has fascinated researchers from numerous disciplines. The painstaking works of pioneers of these last two centuries, such as Rolando, Flourens, Luciani, Babinski, Holmes, Cajal, Larsell, or Eccles, still exert a strong influence in the way we approach cerebellar functions. Advances in genetic studies, detailed molecular and cellular analyses, profusion of brain imaging techniques, emergence of behavioral assessments, and reshaping of models of cerebellar function are generating an immense amount of knowledge. Simultaneously, a better definition of cerebellar disorders encountered in the clinic is emerging. The essentials of a trans-disciplinary blending are expanding. The analysis of the literature published these last two decades indicates that the gaps between domains of research are vanishing. The launch of the society for research on the cerebellum (SRC) illustrates how cerebellar research is burgeoning. This special issue gathers the contributions of the inaugural conference of the SRC dedicated to the mechanisms of cerebellar function. Contributions were brought together around five themes: (1) cerebellar development, death, and regeneration; (2) cerebellar circuitry: processing and function; (3) mechanisms of cerebellar plasticity and learning; (4) cerebellar function: timing, prediction, and/or coordination?; (5) anatomical and disease perspectives on cerebellar function.The Cerebellum 11/2008; 7(4):505-16. DOI:10.1007/s12311-008-0063-7 · 2.72 Impact Factor