Increased expression and colocalization of GAP43 and CASP3 after brain ischemic lesion in mouse.
GAP43 is a protein involved in neurite outgrowth during development and axon regeneration reflecting its presynaptic localization in developing neurons. Recently, it has been demonstrated that GAP43 is a ligand of CASP3 involved in receptor endocytosis and is also localized post-synaptically. In this study, by using a transgenic mouse strain carrying a bioluminescent reporter for GAP43 combined with an in vivo bioluminescence assay for CASP3, we demonstrated that one day after brain ischemic lesion and, even more pronounced, four days after stroke, expression of both CASP3 and Gap43 in neurons increased more than 40 times. The in vivo approach of CASP3 and GAP43 colocalization imaging was further validated and quantified by immunofluorescence. Importantly, in 82% of GAP43 positive cells, colocalization with CASP3 was present. These findings suggested that one and four days after stroke CASP3 expression, not necessarily associated with neuronal death, increased and suggested that CASP3 and GAP43 might be part of a common molecular pathway involved in early response to ischemic events occurring after onset of stroke.
Laboratory for Neurogenetics and Developmental Genetics, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 12, Zagreb HR-10000, Croatia. Electronic address: dgorup@hiim.hr.
Dunja
D
Gorup
Laboratory for Neurogenetics and Developmental Genetics, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 12, Zagreb HR-10000, Croatia. Electronic address: ibohacek@hiim.hr.
Ivan
I
Bohaček
Laboratory for Neurogenetics and Developmental Genetics, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 12, Zagreb HR-10000, Croatia. Electronic address: tenamilicevic@gmail.com.
Tena
T
Miličević
Laboratory for Neurogenetics and Developmental Genetics, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 12, Zagreb HR-10000, Croatia; Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Brussels B-1070, Belgium. Electronic address: rpochet@ulb.ac.be.
Roland
R
Pochet
Laboratory for Stem Cells, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 12, Zagreb HR-10000, Croatia. Electronic address: dinko.mitrecic@mef.hr.
Dinko
D
Mitrečić
Research Centre of Institute universitaire en santé mentale and Department of Psychiatry and Neuroscience, Laval University, Quebec City G1J2G3a, Canada. Electronic address: jasna.kriz@fmed.ulaval.ca.
Jasna
J
Križ
Laboratory for Neurogenetics and Developmental Genetics, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 12, Zagreb HR-10000, Croatia. Electronic address: srecko.gajovic@hiim.hr.
Srećko
S
Gajović
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D019922:GAP-43 Protein / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D013997:Time Factors
D019922:GAP-43 Protein; C505409:Casp3 protein, mouse; D053148:Caspase 3
Bioluminescence; Brain ischemia; CASP3; GAP43; tMCAO