Clusterin/ApoJ expression is associated with neuronal apoptosis in the olfactory mucosa of the adult mouse.
The molecular events orchestrating neuronal degeneration and regeneration remain poorly understood. Attempts at identifying genes specifically expressed during these processes, have constantly led to the (re)isolation of the clusterin/ApoJ gene, whose expression is highly reactive to injury in a wide variety of tissues. To get insight into the function of clusterin in neuron loss, we have assessed in detail the clusterin gene expression in an experimental model of neurodegeneration, using the peripheral olfactory system of adult mouse. The sensory neurons of olfactory nasal mucosa can be massively induced to degenerate in vivo, by surgical removal of their only synaptic target: the olfactory bulb. We have previously shown that this neuron loss results from a near-synchronized induction of apoptosis genetic programs. We present here evidence that clusterin gene expression is tightly correlated to the onset of neuronal apoptoses in lesioned olfactory mucosae. The simultaneous preparation of DNA and RNA from the same tissue samples reveals that a strong clusterin mRNA accumulation coincides with the wave of nucleosome-sized DNA fragmentation. However, double detection of apoptotic nuclei by the TUNEL method and of clusterin messengers by in situ hybridization revealed that the clusterin gene expression is not induced in dying neurons, but in the glial sheath surrounding the axon bundles of degenerating olfactory neurons. Clusterin immunocytochemistry reveals that the clusterin protein accumulates not only in these producing cells, but also in the olfactory epithelium, suggesting the possibility of clusterin internalization by cells located at a distance from the synthesis loci. In view of this localization and of the activities of the clusterin protein reported so far, possible functions of clusterin in nervous plasticity are discussed.
Michel
D
D
Laboratoire de Biologie Moléculaire et Cellulaire, UMR49 CNRS-Ecole Normale Supérieure de Lyon, France.
Moyse
E
E
Trembleau
A
A
Jourdan
F
F
Brun
G
G
D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051152:Clusterin; D003169:Complement Inactivator Proteins / Q000032:analysis / Q000235:genetics*; D003714:Denervation; D005786:Gene Expression Regulation / Q000502:physiology; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones; D009474:Neurons / Q000737:chemistry / Q000166:cytology*; D009830:Olfactory Bulb / Q000601:surgery; D009831:Olfactory Mucosa / Q000166:cytology* / Q000294:innervation / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis
C495243:Clu protein, mouse; D051152:Clusterin; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D018832:Molecular Chaperones; D012333:RNA, Messenger