title: Neuronal injury marker ATF-3 is induced in primary afferent neurons of monoarthritic rats.
abstract: Activating transcription factor 3 (ATF-3) expression has been associated with several signaling pathways implicated in cellular stress response in many cell types and is usually regarded as a neuronal damage marker in dorsal root ganglia (DRG). We investigated ATF-3 expression in primary afferents in the monoarthritic (MA) model of chronic inflammatory joint pain. Immunohistochemistry revealed that ATF-3 is highly induced mainly in small and medium neurons, especially at 2 and 4 days of MA in L(5) DRGs. Colocalization with calcitonin gene-related peptide (CGRP) and isolectin B4 (IB4) demonstrated that ATF-3-immunoreactive cells are mainly peptidergic. The lack of significant differences in ATF-3 and pAkt colocalization indicated that ATF-3 is probably not involved in a pAkt-mediated survival pathway. Anti-inflammatory (ketoprofen) administration failed to reverse ATF-3 induction in MA rats, but significantly increased CGRP expression. These data suggest that ATF-3 expression is definitely involved in MA, actually marking injured neurons. Some degree of neuronal damage seems to occur right from the first days of disease, mainly affecting small-to-medium peptidergic neurons. The intra-articular injection of complete Freund's adjuvant and the generation of a neuroinflammatory environment seem to be the plausible explanation for the local nerve damage.
authors.affiliation: Departamento de Biologia Experimental, Faculdade de Medicina do Porto e Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Nascimento
authors.forename: Daniel Humberto
authors.initials: DH
authors.lastname: Pozza
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Castro-Lopes
authors.forename: Fani Lourença
authors.initials: FL
authors.lastname: Neto
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism*; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D007150:Immunohistochemistry; D037102:Lectins / Q000378:metabolism; D008297:Male; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D053675:Versicans
chemical_list: D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D015415:Biomarkers; D006023:Glycoproteins; D037102:Lectins; C508324:Vcan protein, rat; D053675:Versicans; D051057:Proto-Oncogene Proteins c-akt; D015740:Calcitonin Gene-Related Peptide