title: Dynamic changes in the expression pattern of ecto-5'-nucleotidase in the rat model of cortical stab injury.
abstract: Traumatic injury induces massive release of ATP in the extracellular space, where it influences numerous aspects of neuronal, astrocytic, and microglial responses to injury by activating P2X and P2Y receptors. The extracellular ATP actions are controlled by the ectonucleotidase enzyme pathway, which hydrolyses ATP to adenosine at all neuronal and nonneuronal cell types. Adenosine activates its P1 receptors, which have important neuroprotective roles. The rate-limiting enzyme in the ectonucleotidase pathway is ecto-5'-nucleotidase (e-5NT), which catalyzes the final step of dephosphorylation of AMP to adenosine. The aim of the present study was to characterize the expression pattern and cellular distribution of e-5NT in the perilesioned cortex at 4 hr and 1, 2, 7, and 15 days after unilateral cortical stab injury (CSI). Immunoblot and immunohistochemical studies showed that overall e-5NT expression was lower 4 hr and 1 day postinjury and then gradually increased above the control levels. Double-immunofluorescence studies further showed in control tissue the presence of the enzyme in the membranes surrounding neuronal somata and apical dendrites and less frequently in astrocytes. CSI caused a rapid (after 4 hr) and irreversible loss of the enzyme from neurons, accounting for a decrease in the overall enzyme expression. This was accompanied with a gradual increase in e-5NT-positive astrocytes, accounting for up-regulation of the enzyme levels in the injured area. Thus, CSI induced dynamic changes in the expression pattern of e-5NT that modify the ATP/adenosine ratio and the extent of P1 and P2 receptors activation and, therefore, outcome of the pathological processes after CSI.
authors.affiliation: Department for Neurobiology, Institute for Biological Research Sinisa Stankovic, University Belgrade, Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Bjelobaba
authors.forename: Ana
authors.initials: A
authors.lastname: Parabucki
authors.forename: Irena
authors.initials: I
authors.lastname: Lavrnja
authors.forename: Danijela
authors.initials: D
authors.lastname: Stojkov
authors.forename: Sanja
authors.initials: S
authors.lastname: Dacic
authors.forename: Sanja
authors.initials: S
authors.lastname: Pekovic
authors.forename: Ljubisa
authors.initials: L
authors.lastname: Rakic
authors.forename: Mirjana
authors.initials: M
authors.lastname: Stojiljkovic
authors.forename: Nadezda
authors.initials: N
authors.lastname: Nedeljkovic
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D005904:Glial Fibrillary Acidic Protein; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D015720:5'-Nucleotidase; D010751:Phosphopyruvate Hydratase