NeuropharmacologyDeprivation of sensory inputs to the olfactory bulb up-regulates cell death and proliferation in the subventricular zone of adult mice
Section snippets
Animals
Adult male C57Bl/6J mice (IFFA CREDO, L’Arbresles, France) aged 8–12 weeks at the beginning of the experiment were used. All animals were housed under a 12 h light/dark cycle with food and water available ad libitum. All efforts were made to minimize the number of animals used and their suffering during the experimental procedure in accordance with the European Community Council Directive of November 24, 1986 (86/609/EEC), and the French Ethical Committee. Mice were subjected to unilateral
Axotomy-induced reduction in OE thickness and recovery
The thickness of the OE was reduced by 23±4% (mean±S.E.M., P<0.0001) 6 days post-axotomy (Fig. 2) compared with the non-operated side, indicative of the massive death of mature disconnected ORNs. From 12–30 days post-axotomy, the thickness of the OE on the lesioned side slowly recovered and returned to normal values at 60 days post-axotomy. The thickness of the OE in sham-operated controls was not statistically different from the non-operated side of axotomized animals.
Olfactory axotomy increases cell death in the RMS-OB, RMS and SVZ
Apoptosis was measured
Discussion
In the present report, cell death and proliferation increased in the SVZ, RMS and RMS-OB during the first 2 weeks following olfactory deafferentation by axotomy and returned to control values 1 month after deafferentation. These changes closely followed the temporal pattern of ORNs death and regeneration. In addition, it has been shown that responses to odorants can be recorded from MOB cells starting 1 month post-axotomy (Costanzo, 1985). These data strongly suggest that the changes in cell
Conclusion
Three main findings arise from the present study. (1) Following axotomy cell death in the RMS targets migrating neuroblasts suggesting that they depend upon olfactory inputs for their survival. (2) Proliferation is enhanced following axotomy with a spatio-temporal pattern which only partly mirrors increased cell death. This observation suggests that proliferation does not only balance cell death but may be governed by a larger set of mechanisms. (3) Evidence is provided for the existence of a
Acknowledgements
This work was supported by Région Rhône-Alpes (Program Emergence) and Fondation Roudnitska (Fellowship to N.M.). We thank Dr. G. Grenningloh for the gift of the anti-stathmin antibody. Many thanks to Drs. Giannetti, Marcel and Pellier for helpful discussions. We are grateful to Dr. P. M. Lledo for comments on the manuscript.
References (66)
- et al.
Mapping of the distribution of polysialylated neural cell adhesion molecule through-out the central nervous system of the adult ratan immunohistochemical study
Neuroscience
(1992) - et al.
Apoptosis in the rostral migratory stream of the developing rat
Dev Brain Res
(1996) - et al.
Neurogenesis persists in the subependymal layer of the adult mouse brain
Neurosci Lett
(1993) - et al.
Odor deprivation leads to reduced neurogenesis and reduced neuronal survival in the olfactory bulb of the adult mouse
Neuroscience
(1994) Comparison of neurogenesis and cell replacement in the hamster olfactory system with and without a target (olfactory bulb)
Brain Res
(1984)Neural regeneration and functional reconnection following olfactory nerve transection in hamster
Brain Res
(1985)- et al.
The effects of variable periods of functional deprivation on the olfactory bulb development in rats
Exp Neurol
(1997) - et al.
Quantification of the effects of long-term unilateral naris closure on the olfactory bulbs of adult mice
Brain Res
(1991) - et al.
Cell death in regenerating populations of neurons in BDNF mutant mice
Mol Brain Res
(2000) Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone
Neuron
(1993)