Bcl-2 and Bax proteins are increased in neocortical but not in thalamic apoptosis following devascularizing lesion of the cerebral cortex in the rat: an immunohistochemical study.
The hypothesis that devascularization of somatosensory and motor cortex causes apoptosis in infarcted regions and in the linked thalamic nuclei was evaluated. To unravel whether Bcl-related proteins, known to regulate apoptosis, participate in neuronal and glial responses to devascularization, we analyzed immunohistochemically the distribution and intensity of staining of Bcl-2 and Bax proteins at different time points after lesion. Both early (up to 6 h) and late (1-7 days) responses were studied. Devascularization led to rapid (within hours) apoptosis in the cortex and to a delayed (within 3-7 days) apoptosis in thalamic nuclei. In control groups, Bcl-2 and Bax immunoreactivity (IR) was detected in neurons and oligodendrocytes but not in astrocytes or microglia. Following devascularization, Bcl-2 IR and Bax IR increased in neurons before the onset of the apoptosis. In the ischemic focus, the increase reached maximal values 3 h after the lesion. The increase was of slower onset in the penumbra zone (24 h and after), a region in which both proteins were induced in astrocytes also. The change of Bax IR intensity exceeded four times that of Bcl-2 at all time points investigated, indicating a diminution of Bcl-2/Bax ratio that may direct neurons to apoptotic pathway. In numerous neurons, an increase of IR in the cytoplasm was accompanied by induction of nuclear staining. No changes of Bcl-2 and Bax IR were found in thalamic nuclei. Our results point to different mechanisms underlying apoptosis of cortical and thalamic neurons. Nuclear appearance of Bcl-2 and Bax suggests they possess regulatory role of gene expression changes triggered by cortical infarct.
Sulejczak
Dorota
D
Laboratory for Reinnervation Processes, Department of Neurophysiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
Czarkowska-Bauch
Julita
J
Macias
Matylda
M
Skup
Malgorzata
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D019579:Neocortex / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling / Q000379:methods; D013788:Thalamus / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D005904:Glial Fibrillary Acidic Protein; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D010751:Phosphopyruvate Hydratase