Antonio Giuditta

Emeritus Professor of Physiology

Name Antonio
Surname Giuditta
Institution University of Naples – Federico II
E-Mail giuditta@unina.it
Address Department of Biology, University of Naples Federico II, Via Cinthia, 80126, Naples, Italy
Antonio Giuditta

Member PUBLICATIONS

  • Synaptic mRNAs are modulated by learning.

    Publication Date: 01/07/2009 on Journal of neuroscience research
    by Ferrara E, Cefaliello C, Eyman M, De Stefano R, Giuditta A, Crispino M
    DOI: 10.1002/jnr.22037

    We have recently demonstrated that brain plastic events significantly modify synaptic protein synthesis measured by the incorporation of [(35)S]methionine in brain synaptosomal proteins. Notably, in rats learning a two-way active avoidance task, the local synthesis of two synaptic proteins was selectively enhanced. Because this effect may be attributed to transcriptional modulation, we used reverse transcriptase-polymerase chain reaction methods to determine the content of discrete synaptosomal mRNAs in rats exposed to the same training protocol. Correlative analyses between behavioral responses and synaptosomal mRNA content showed that GAT-1 mRNA (a prevalent presynaptic component) correlates with avoidances and escapes in rat cerebellum, while glial fibrillary acid protein mRNA (an astrocytic component) correlates with freezings in cerebellum and cerebral cortex. These observations support the hypothesis that synaptic protein synthesis may be transcriptionally regulated. The cellular origin of synaptic transcripts is briefly discussed, with special regard to those present at large distances from neuron somas.

  • Protein synthesis in nerve terminals and the glia-neuron unit.

    Publication Date: 01/01/2009 on Results and problems in cell differentiation
    by Crispino M, Cefaliello C, Kaplan B, Giuditta A
    DOI: 10.1007/400_2009_9

    The progressive philogenetic lengthening of axonal processes and the increase in complexity of terminal axonal arborizations markedly augmented the demands of the neuronal cytoplasmic mass on somatic gene expression. It is proposed that in an adaptive response to this challenge, novel gene expression functions developed in the axon compartment, consisting of axonal and presynaptic translation systems that rely on the delivery of transcripts synthesized in adjacent glial cells. Such intercellular mode of gene expression would allow more rapid plastic changes to occur in spatially restricted neuronal domains, down to the size of individual synapses. The cell body contribution to local gene expression in well-differentiated neurons remains to be defined. The history of this concept and the experimental evidence supporting its validity are critically discussed in this article. The merit of this perspective lies with the recognition that plasticity events represent a major occurrence in the brain, and that they largely occur at synaptic sites, including presynaptic endings.

  • Identification of a synaptosome-associated form of BAG3 protein.

    Publication Date: 01/10/2008 on Cell cycle (Georgetown, Tex.)
    by Bruno AP, Festa M, Dal Piaz F, Rosati A, Turco MC, Giuditta A, Marzullo L
    DOI: 10.4161/cc.7.19.6774
  • Local gene expression in axons and nerve endings: the glia-neuron unit.

    Publication Date: 01/04/2008 on Physiological reviews
    by Giuditta A, Chun JT, Eyman M, Cefaliello C, Bruno AP, Crispino M
    DOI: 10.1152/physrev.00051.2006

    Neurons have complex and often extensively elongated processes. This unique cell morphology raises the problem of how remote neuronal territories are replenished with proteins. For a long time, axonal and presynaptic proteins were thought to be exclusively synthesized in the cell body, which delivered them to peripheral sites by axoplasmic transport. Despite this early belief, protein has been shown to be synthesized in axons and nerve terminals, substantially alleviating the trophic burden of the perikaryon. This observation raised the question of the cellular origin of the peripheral RNAs involved in protein synthesis. The synthesis of these RNAs was initially attributed to the neuron soma almost by default. However, experimental data and theoretical considerations support the alternative view that axonal and presynaptic RNAs are also transcribed in the flanking glial cells and transferred to the axon domain of mature neurons. Altogether, these data suggest that axons and nerve terminals are served by a distinct gene expression system largely independent of the neuron cell body. Such a local system would allow the neuron periphery to respond promptly to environmental stimuli. This view has the theoretical merit of extending to axons and nerve terminals the marginalized concept of a glial supply of RNA (and protein) to the neuron cell body. Most long-term plastic changes requiring de novo gene expression occur in these domains, notably in presynaptic endings, despite their intrinsic lack of transcriptional capacity. This review enlightens novel perspectives on the biology and pathobiology of the neuron by critically reviewing these issues.

  • Natural computing and biological evolution: a new paradigm.

    Publication Date: 01/01/2008 on Rivista di biologia
    by Giuditta A

    After a brief outline of the available hypotheses on the mechanism of biological evolution, attention is called on the global nature of the variations leading to the generation of new species. Integrated changes may hardly be attributed to beneficial random mutations of single traits even if assisted by a phylogenetic elimination of poorly adapted individuals. Rather, integrated variations are likely to reflect the outcome of cybernetic algorithms (natural computing) operating on organism's resources and impending environmental changes. As all organisms are endowed with computing capacities that modulate and integrate ontogenetic development and maintenance of biological functions, structures, and behaviors, these capacities are assumed to have moulded the evolutionary variations of organisms, and their transfer to the progeny.

  • Axonal and presynaptic RNAs are locally transcribed in glial cells.

    Publication Date: 01/05/2007 on Rivista di biologia
    by Giuditta A, Chun JT, Eyman M, Cefaliello C, Bruno AP, Crispino M

    In the last few years, the long-standing opinion that axonal and presynaptic proteins are exclusively derived from the neuron cell body has been substantially modified by the demonstration that active systems of protein synthesis are present in axons and nerve terminals. These observations have raised the issue of the cellular origin of the involved RNAs, which has been generally attributed to the neuron soma. However, data gathered in a number of model systems indicated that axonal RNAs are synthesized in the surrounding glial cells. More recent experiments on the perfused squid giant axon have definitively proved that axoplasmic RNAs are transcribed in periaxonal glia. Their delivery to the axon occurs by a modulatory mechanism based on the release of neurotransmitters from the stimulated axon and on their binding to glial receptors. In additional experiments on squid optic lobe synaptosomes, presynaptic RNA has been also shown to be synthesized locally, presumably in nearby glia. Together with a wealth of literature data, these observations indicate that axons and nerve terminals are endowed with a local system of gene expression that supports the maintenance and plasticity of these neuronal domains.

  • Synaptosomal protein synthesis is selectively modulated by learning.

    Publication Date: 09/02/2007 on Brain research
    by Eyman M, Cefaliello C, Ferrara E, De Stefano R, Crispino M, Giuditta A
    DOI: 10.1016/j.brainres.2006.11.025

    Synaptosomes from rat brain have long been used to investigate the properties of synaptic protein synthesis. Comparable analyses have now been made in adult male rats trained for a two-way active avoidance task to examine the hypothesis of its direct participation in brain plastic events. Using Ficoll-purified synaptosomes from neocortex, hippocampus and cerebellum, our data indicate that the capacity of synaptosomal protein synthesis and the specific activity of newly synthesized proteins were not different in trained rats in comparison with home-caged control rats. On the other hand, the synthesis of two proteins of 66.5 kDa and 87.6 kDa separated by SDS-PAGE and analyzed by quantitative densitometry was selectively enhanced in trained rats. In addition, the synthesis of the 66.5 kDa protein, but not of the 87.6 kDa protein, correlated with avoidances and escapes and inversely correlated with freezings in the neocortex, while in the cerebellum it correlated with avoidances and escapes. The data demonstrate the participation of synaptic protein synthesis in plastic events of behaving rats, and the selective, region-specific modulation of the synthesis of a synaptic 66.5 kDa protein by the newly acquired avoidance response and by the reprogramming of innate neural circuits subserving escape and freezing responses.

  • Local synthesis of axonal and presynaptic RNA in squid model systems.

    Publication Date: 01/01/2007 on The European journal of neuroscience
    by Eyman M, Cefaliello C, Ferrara E, De Stefano R, Lavina ZS, Crispino M, Squillace A, van Minnen J, Kaplan BB, Giuditta A
    DOI: 10.1111/j.1460-9568.2007.05304.x

    The presence of active systems of protein synthesis in axons and nerve endings raises the question of the cellular origin of the corresponding RNAs. Our present experiments demonstrate that, besides a possible derivation from neuronal cell bodies, axoplasmic RNAs originate in periaxonal glial cells and presynaptic RNAs derive from nearby cells, presumably glial cells. Indeed, in perfused squid giant axons, delivery of newly synthesized RNA to the axon perfusate is strongly stimulated by axonal depolarization or agonists of glial glutamate and acetylcholine receptors. Likewise, incubation of squid optic lobe slices with [3H]uridine leads to a marked accumulation of [3H]RNA in the large synaptosomes derived from the nerve terminals of retinal photoreceptor neurons. As the cell bodies of these neurons lie outside the optic lobe, the data demonstrate that presynaptic RNA is locally synthesized, presumably by perisynaptic glial cells. Overall, our results support the view that axons and presynaptic regions are endowed with local systems of gene expression which may prove essential for the maintenance and plasticity of these extrasomatic neuronal domains.

  • Brain and behavioural evidence for rest-activity cycles in Octopus vulgaris.

    Publication Date: 25/09/2006 on Behavioural brain research
    by Brown ER, Piscopo S, De Stefano R, Giuditta A
    DOI: 10.1016/j.bbr.2006.05.009

    Octopus vulgaris maintained under a 12/12h light/dark cycle exhibit a pronounced nocturnal activity pattern. Animals deprived of rest during the light period show a marked 'rebound' in activity in the following 24h. 'Active' octopuses attack faster than 'quiet' animals and brain activity recorded electrically intensifies during 'quiet' behaviour. Thus, in Octopus as in vertebrates, brain areas involved in memory or 'higher' processes exhibit 'off-line' activity during rest periods.

  • Local Synthesis of Presynaptic RNA in Squid Optic Lobe Slices.

    Publication Date: 01/10/2004 on The Biological bulletin
    by Giuditta A, Eyman M, Cefaliello C, Ferrara E, Kaplan BB, Lavina ZS, De Stefano R
    DOI: 10.1086/BBLv207n2p156a