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BB14, a Nerve Growth Factor (NGF)-like peptide shown to be effective in reducing reactive astrogliosis and restoring synaptic homeostasis in a rat model of peripheral nerve injury (108 visite)

Cirillo G, Colangelo AM, Bianco MR, Cavaliere C, Zaccaro L, Sarmientos P, Alberghina L, Papa M

Biotechnology Advances (ISSN: 0734-9750), 2012 Jan; 30(1): 223-232.



Tipo di articolo: Journal Article,

Impact factor: 9.599, Impact factor a 5 anni: 11.85

Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-84855746317&partnerID=40&md5=373569bf397db8f269323fef5c3174f8

Parole chiave: Nerve Injury, Neuro-Glial Network, Ngf-Like Peptide, Reactive Astrocytosis, Synaptic Homeostasis, Astrogliosis, Beneficial Effects, Gabaergic, Glutamate Transporters, Glutathiones, Hyperalgesia, Immunohistochemical Analysis, Molecular Changes, Nerve Growth Factor, Nerve Injuries, Neurodegenerative Disorders, Neuropathic Pain, Neuroplastic Changes, Neuroprotection, Pathological Conditions, Peptidomimetics, Peripheral Nerves, Rat Model, Sciatic Nerves, Spinal Cords, Therapeutic Agents, Dosimetry, Neurodegenerative Diseases, Physiology, Analgesic Agent, Glutamic Acid, Glycine, Biomarker, Correlation, Inhibitor, Animal, Article, Chemistry, Disease Model, Drug Effect, Immunohistochemistry, Metabolism, Peripheral Nerve Injury, Spinal Cord Injury, Sprague Dawley Rat, Peripheral Nerve Injuries, Sprague-Dawley, Spinal Cord Injuries, Synapses, Rattus,

Affiliazioni:

*** IBB - CNR ***
Laboratory of Morphology of Neural Networks, Department of Medicina Pubblica Clinica e Preventiva, Second University of Napoli, 80138 Napoli, Italy
Laboratory of Neuroscience R. Levi-Montalcini, Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milano, Italy
PRIMM Srl, Milano, Italy
Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, Department of Biological Sciences, Univ. of Napoli Federico II and Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche, 80138 Napoli, Italy



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Allen, N. J., Barres, B. A., Neuroscience: Glia - more than just brain glue (2009) Nature, 457, pp. 675-67

Apfel, S. C., Nerve growth factor for the treatment of diabetic neuropathy: what went wrong, what went right, and what does the future hold? (2002) Int Rev Neurobiol, 50, pp. 393-413

Bai, Y. H., Takemitsu, M., Atsuta, Y., Matsuno, T., Peripheral mononeuropathy induced by loose ligation of the sciatic nerve in the rat: behavioral, electrophysiological and histopathologic studies (1999) Exp Anim, 48, pp. 87-94

Bruno, M. A., Cuello, A. C., Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade (2006) Proc Natl Acad Sci USA, 103, pp. 6735-6740

Chao, M. V., Rajagopal, R., Lee, F. S., Neurotrophin signalling in health and disease (2006) Clin Sci, 2, pp. 167-173

Chaplan, S. R., Bach, F. W., Pogrel, J. W., Chung, J. M., Yaksh, T. L., Quantitative assessment of tactile allodynia in the rat paw (1994) J Neurosci Methods, 53, pp. 55-63

Colangelo, A. M., Bianco, M. R., Vitagliano, L., Cavaliere, C., Cirillo, G., De Gioia, L., A new nerve growth factor-mimetic peptide active on neuropathic pain in rats (2008) J Neurosci, 28, pp. 2698-2709

Cuello, A. C., Bruno, M. A., Bell, K. F., NGF-cholinergic dependency in brain aging, MCI and Alzheimer's disease (2007) Curr Alzheimer Res, 4, pp. 351-358

Hamilton, N. B., Attwell, D., Do astrocytes really exocytose neurotransmitters? (2010) Nat Rev Neurosci, 11, pp. 227-238

Harrington, A. W., Leiner, B., Blechschmitt, C., Arevalo, J. C., Lee, R., M rl, K., Secreted proNGF is a pathophysiological death-inducing ligand after adult CNS injury (2004) Proc Natl Acad Sci USA, 101, pp. 6226-6230

Lobsiger, C. S., Cleveland, D. W., Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease (2007) Nat Neurosci, 10, pp. 1355-1360

Longo, F. M., Manthorpe, M., Xie, Y. M., Varon, S., Synthetic NGF peptide derivatives prevent neuronal death via a p75 receptor-dependent mechanism (1997) J Neurosci Res, 48, pp. 1-17

Massa, S. M., Yang, T., Xie, Y., Shi, J., Bilgen, M., Joyce, J. N., Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents (2010) J Clin Invest, 120, pp. 1774-1785

McDonald, N. Q., Chao, M. V., Structural determinants of neurotrophin action (1995) J Biol Chem, 270, pp. 19669-19672

Meisner, J. G., Marsh, A. D., Marsh, D. R., Loss of GABAergic interneurons in Laminae I-III of the spinal cord dorsal horn contributes to reduced GABAergic tone and neuropathic pain following spinal cord injury (2010) J Neurotrauma, 27, pp. 729-737

Poduslo, J. F., Curran, G. L., Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF (1996) Mol Brain Res, 36, pp. 280-286

Polg r, E., Todd, A. J., Tactile allodynia can occur in the spared nerve injury model in the rat without selective loss of GABA or GABA (A) receptors from synapses in laminae I-II of the ipsilateral spinal dorsal horn (2008) Neuroscience, 156, pp. 193-202

Ryd n, M., Ib nez, C. F., A second determinant of binding to the p75 neurotrophin receptor revealed by Alanine-Scanning mutagenesis of a conserved loop in Nerve Growth Factor (1997) J Biol Chem, 272, pp. 33085-33091

Shih, A. Y., Erb, H., Sun, X., Toda, S., Kalivas, P. W., Murphy, T. H., Cystine/glutamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation (2006) J Neurosci, 26, pp. 10514-10523

Todd, A. J., Neuronal circuitry for pain processing in the dorsal horn (2010) Nat Rev Neurosci, 12, pp. 823-836

Tuszynski, M. H., Thal, L., Pay, M., Salmon, D. P. U. H. S., Bakay, R., Patel, P., Blesch, A., Conner, J., A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease (2005) Nat Med, 11, pp. 551-555

Zaccaro, M. C., Lee, H. B., Pattarawarapan, M., Xia, Z., Caron, A., L'Heureux, P. J., Selective small molecule peptidomimetic ligands of TrkC and TrkA receptors afford discrete or complete neurotrophic activities (2005) Chem Biol, 12, pp. 1015-1028



Peptidomimetics hold a great promise as therapeutic agents for neurodegenerative disorders. We previously described a Nerve Growth Factor (NGF)-like peptide, now named BB14, which was found to act as a strong TrkA agonist and to be effective in the sciatic nerve injury model of neuropathic pain. In this report we present the effects of BB14 in reducing reactive astrocytosis and reverting neuroplastic changes of the glutamate/GABAergic circuitry in the lumbar spinal cord following spared nerve injury (SNI) of the sciatic nerve. Immunohistochemical analysis of spinal cord sections revealed that SNI was associated with increased microglial (Iba1) and astrocytic (GFAP) responses, indicative of reactive gliosis. These changes were paralleled by (i) decreased glial aminoacid transporters (GLT1 and GlyT1) and increased levels of (ii) neuronal glutamate transporter EAAC1, (iii) neuronal vesicular GABA transporter (vGAT) and (iv) the GABAergic neuron marker GAD65/67. A remarkable increase of the Glutamate/GABA ratio and the reduction of glutathione (GSH) levels were also indicative of modifications of glial function in neuroprotection. All these molecular changes were found to be linked to an alteration of endogenous NGF metabolism, as demonstrated by decreased levels of mature NGF, increase of proNGF and increased activity of NGF-degrading methallo-proteinases (MMPs). Biochemical alterations and SNI-related neuropathic behavior, characterized by allodynia and hyperalgesia, were reversed by 7-days i.t, administration of the NGF-like peptide BB14, as well as by increasing endogenous NGF levels by it. infusion of GM6001, a MMPs inhibitor. All together, while confirming the correlation between reactive astrogliosis and perturbation of synaptic circuitry in the SNI model of peripheral nerve injury, these data strongly support the beneficial effect of BB14 in reducing reactive astrogliosis and restoring synaptic homeostasis under pathological conditions linked to alteration of NGF availability and signaling, thereby suggesting a potential role of BB14 as a therapeutic agent. (C) 2011 Published by Elsevier Inc.
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19 Records (18 escludendo Abstract e Conferenze).
Impact factor totale: 78.545 (71.909 escludendo Abstract e Conferenze).
Impact factor a 5 anni totale: 78.291 (74.423 escludendo Abstract e Conferenze).







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Ultima modifica di Marco Comerci in data Thursday 19 March 2015, 16:43:14
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Ultimo aggiornamento: Wednesday 20 February 2019, 11:48:26