title: Astrocytes and Microglia-Mediated Immune Response in Maladaptive Plasticity is Differently Modulated by NGF in the Ventral Horn of the Spinal Cord Following Peripheral Nerve Injury.
abstract: Reactive astrocytes and activated microglia are the key players in several pathophysiologic modifications of the central nervous system. We used the spared nerve injury (SNI) of the sciatic nerve to induce glial maladaptive response in the ventral horn of lumbar spinal cord and examine its role in the remodeling of the tripartite synapse plasticity. Imaging the ventral horn revealed that SNI was associated with both an early microglial and astrocytic activation, assessed, respectively, by analysis of Iba1 and GFAP expression. Microglia, in particular, localized peculiarly surrounding the motor neurons somata. Perineuronal astrocytes, which play a key role in maintaining the homeostasis of neuronal circuitry, underwent a substantial phenotypic change following peripheral axotomy, producing reactive gliosis. The gliosis was associated with the reduction of glial aminoacid transporters (GLT1 and GlyT1) and increase of neuronal glutamate transporter EAAC1. Although the expression of GABAergic neuronal marker GAD65/67 showed no change, glutamate increase, as demonstrated by HPLC analysis, shifted the excitatory/inhibitory balance as showed by the net increase of the glutamate/GABA ratio. Moreover, endogenous NGF levels were altered in SNI animals and not restored by the intrathecal NGF administration. This treatment reverted phenotypic changes associated with reactive astrocytosis, but failed to modify microglia activation. These findings on one hand confirm the correlation between gliopathy and maladaptive plasticity of the spinal synaptic circuitry, on the other hand add new data concerning the complex peculiar behavior of different glial cells in neuronal degenerative processes, defining a special role of microglia in sustaining the inflammatory response.
authors.affiliation: Laboratory of Neuronal Networks, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Via L. Armanni, 5, 80138, Naples, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: De Luca
authors.affiliation: Laboratory of Neuronal Networks, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Via L. Armanni, 5, 80138, Naples, Italy.|SYSBIO, Centre of Systems Biology, University of Milano-Bicocca, Milan, Italy.
authors.forename: Leonilde
authors.initials: L
authors.lastname: Savarese
authors.affiliation: Laboratory of Neuroscience "R. Levi-Montalcini", Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.|SYSBIO, Centre of Systems Biology, University of Milano-Bicocca, Milan, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Colangelo
authors.affiliation: Laboratory of Neuronal Networks, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Via L. Armanni, 5, 80138, Naples, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Bianco
authors.affiliation: Laboratory of Neuronal Networks, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Via L. Armanni, 5, 80138, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cirillo
authors.affiliation: Laboratory of Neuroscience "R. Levi-Montalcini", Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.|SYSBIO, Centre of Systems Biology, University of Milano-Bicocca, Milan, Italy.
authors.forename: Lilia
authors.initials: L
authors.lastname: Alberghina
authors.affiliation: Laboratory of Neuronal Networks, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Via L. Armanni, 5, 80138, Naples, Italy. michele.papa@unina2.it.|SYSBIO, Centre of Systems Biology, University of Milano-Bicocca, Milan, Italy. michele.papa@unina2.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Papa
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005911:Gliosis / Q000473:pathology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007109:Immunity / Q000187:drug effects*; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects*; D059348:Peripheral Nerve Injuries / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D066151:Spinal Cord Ventral Horn / Q000187:drug effects / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D034961:Antigens, Nuclear; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D026901:Membrane Transport Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C546339:Rbfox3 protein, rat; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D020932:Nerve Growth Factor; D005968:Glutamate Decarboxylase
keywords: Glial cells; Maladaptive plasticity; NGF; Spinal cord