Postnatal distribution of cpp32/caspase 3 mRNA in the mouse central nervous system: an in situ hybridization study.
Apoptotic cell death is a major feature of the developing nervous system and of certain neurodegenerative diseases. Various gene effectors and repressors of this type of cell death have been identified. Among them, bcl-xl and bax, which encode for antiapoptotic and proapoptotic proteins, respectively, play major roles during development. The gene cpp32 encodes for the caspase 3 cysteine protease and is a critical mediator of cell death during embryonic development in the mammalian brain. To gain insight into the possible implications of these cell death genes during the postnatal development, we investigated the expression of bax, bcl-xl, and cpp32 mRNAs by in situ hybridization in the mouse brain from birth to adulthood. Whereas bax and bcl-xl mRNAs were expressed widely in neonates and adult mice, our results showed that cpp32 mRNA levels were decreased strongly from 12 postnatal days. From 1 postnatal day to 12 postnatal days, cpp32 mRNA was expressed ubiquitously in all brain nuclei, including areas where neurogenesis occurred. A positive correlation between areas displaying high levels of mRNA and apoptotic nuclei also was shown. In the adult, cpp32 mRNA was restricted to the piriform and entorhinal cortices, the neocortex, and to areas where neurogenesis is observed (e.g., olfactory bulb and dentate gyrus). The same pattern of expression was observed in adult mice over-expressing the antiapoptotic protein Bcl-2. These results demonstrate that the expression of cpp32 mRNA is highly regulated during the mouse postnatal period, leading to a specific distribution in the adult central nervous system. Moreover, the prevention of cell death by Bcl-2 likely is not linked to the regulation of caspase mRNA levels.
de Bilbao
F
F
Department of Psychiatry, University Hospital of Geneva, Switzerland. fabienne.debilbao@medecine.unige.ch
Guarin
E
E
Nef
P
P
Vallet
P
P
Giannakopoulos
P
P
Dubois-Dauphin
M
M
D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D053148:Caspase 3; D020169:Caspases / Q000235:genetics*; D004792:Enzyme Precursors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000502:physiology*; D009412:Nerve Fibers / Q000201:enzymology; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D010761:Phosphorus Radioisotopes; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis
D004792:Enzyme Precursors; D010761:Phosphorus Radioisotopes; D019253:Proto-Oncogene Proteins c-bcl-2; D015347:RNA Probes; D012333:RNA, Messenger; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases