title: Neuronal apoptosis in the striatum of rats treated with 3-nitropropionic acid is not triggered by cell-cycle re-entry.
abstract: Although terminally differentiated neurons lack the capacity to undergo cell division, they retain the capacity to reactivate the cell cycle. This reactivation, however, has been linked to the degeneration of neurons in many experimental models of neurodegenerative disease and in post-mortem brains of affected patients. Expression of markers of the G1 phase and apoptotic neurons has been detected in the striatal lesion of rats treated with 3-nitropropionic acid (3-NPA). Here we examined whether neuronal apoptosis induced by 3-NPA was mediated by the reactivation of the cell cycle. To this end, we studied whether TUNEL-positive neurons expressed the G1-phase markers cyclin-dependent kinase 4 (CDK4) and cyclin D (CyD). In addition, we also evaluated the neuronal expression of pRb and Ki67 antigens, both of which are involved in the regulation of cell-cycle progression. In 3-NPA-treated rats, CDK4 and CyD were not detected in TUNEL-positive neurons, but they were expressed in neurons in the core of the lesion, which were assumed to be in a more advanced stage of degeneration, since they had weaker NeuN staining and lacked Hoechst staining. In addition, injured neurons in the striatal lesion of 3-NPA-treated rats had lost the constitutive expression of pRb and Ki67 that we had detected in control animals. Taken together, these results indicate that neuronal apoptosis in the striatal lesion of 3-NPA-treated rats was not triggered by cell-cycle re-entry, and we conclude that expression of G1 markers may be considered an aberrant survival response, with no relation to the mechanisms of apoptosis.
authors.affiliation: Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII s/n., E-08028 Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Duran-Vilaregut
authors.forename: Gemma
authors.initials: G
authors.lastname: Manich
authors.forename: Jaume
authors.initials: J
authors.lastname: del Valle
authors.forename: Mercè
authors.initials: M
authors.lastname: Pallàs
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
authors.forename: Carme
authors.initials: C
authors.lastname: Pelegrí
authors.forename: Jordi
authors.initials: J
authors.lastname: Vilaplana
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D056741:Cyclin D / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009574:Nitro Compounds / Q000633:toxicity*; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016160:Retinoblastoma Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D056741:Cyclin D; D019394:Ki-67 Antigen; D009574:Nitro Compounds; D011422:Propionates; D016160:Retinoblastoma Protein; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4; C015392:3-nitropropionic acid