摘要
Journal of Comparative NeurologyVolume 431, Issue 3 p. 311-319 Article Cell death in the developing and sensory-deprived rat olfactory bulb Brian K. Fiske, Brian K. Fiske Neuroscience Program, University of Virginia, Charlottesville, Virginia 22903Search for more papers by this authorPeter C. Brunjes, Corresponding Author Peter C. Brunjes [email protected] Neuroscience Program, University of Virginia, Charlottesville, Virginia 22903 Department of Psychology, University of Virginia, Charlottesville, Virginia 22903Department of Psychology, University of Virginia, P.O. Box 400400, Charlottesville, VA 22904Search for more papers by this author Brian K. Fiske, Brian K. Fiske Neuroscience Program, University of Virginia, Charlottesville, Virginia 22903Search for more papers by this authorPeter C. Brunjes, Corresponding Author Peter C. Brunjes [email protected] Neuroscience Program, University of Virginia, Charlottesville, Virginia 22903 Department of Psychology, University of Virginia, Charlottesville, Virginia 22903Department of Psychology, University of Virginia, P.O. Box 400400, Charlottesville, VA 22904Search for more papers by this author First published: 01 February 2001 https://doi.org/10.1002/1096-9861(20010312)431:3<311::AID-CNE1072>3.0.CO;2-7Citations: 71Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Cell death is ubiquitous in the developing brain and an important regulator of cell number. The olfactory bulb, the first central relay for information from the nose, is a particularly appropriate region for studying cell death. The bulb is constantly infused with new cells, has a strictly organized anatomy, and cell survival is known to depend on levels of afferent activation. The present study examined patterns of cell death in both the normally developing and sensory-deprived rat olfactory bulb terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL). In control pups, TUNEL-labeled profiles were high at postnatal day 5 (P5, day of birth = P0), but then decreased rapidly to constant levels. In contrast, blocking airflow through half of the nasal cavity by surgically closing an external naris on P1 resulted in a gradual increase in TUNEL-positive figures within the ipsilateral olfactory bulb by P20, with the effects being seen in the mitral and granule cell layers until at least P60. The effect was largely age dependent, because subjects occluded from P30 to P60 showed only slight increases in cell death. Furthermore, although interlaminar differences were encountered, the pattern of cell death appeared uniform over much of the bulb. Finally, reopening occluded nares decreased cell death levels to control values, suggesting an inverse relationship between the level of olfactory function and the extent of cell death. Thus, the data indicate that cell death is prevalent in the normal olfactory bulb, and that it is directly regulated by the level of olfactory function. J. Comp. Neurol. 431:311–319, 2001. © 2001 Wiley-Liss, Inc. LITERATURE CITED Altman J. 1969a. Autoradiographic and histological studies of postnatal neurogenesis. III. Dating the time of production and onset of differentiation of cerebellar microneurons in rats. J Comp Neurol 136: 269–293. 10.1002/cne.901360303 CASPubMedWeb of Science®Google Scholar Altman J. 1969b. Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol 137: 433–457. 10.1002/cne.901370404 CASPubMedWeb of Science®Google Scholar Bayer SA. 1980. Development of the hippocampal region in the rat. I. Neurogenesis examined with 3H-thymidine autoradiography. J Comp Neurol 190: 87–114. 10.1002/cne.901900107 CASPubMedWeb of Science®Google Scholar Bayer SA. 1983. 3H-thymidine-radiographic studies of neurogenesis in the rat olfactory bulb. Exp Brain Res 50: 329–340. 10.1007/BF00239197 PubMedWeb of Science®Google Scholar Benson TE, Ryugo DK, Hinds JW. 1984. Effects of sensory deprivation on the developing mouse olfactory system: a light and electron microscopic, morphometric analysis. J Neurosci 4: 638–653. CASPubMedWeb of Science®Google Scholar Betarbet R, Zigova T, Bakay RA, Luskin MB. 1996. Dopaminergic and GABAergic interneurons of the olfactory bulb are derived from the neonatal subventricular zone. Int J Dev Neurosci 14: 921–930. 10.1016/S0736-5748(96)00066-4 CASPubMedWeb of Science®Google Scholar Brunjes PC. 1994. Unilateral naris closure and olfactory system development. Brain Res Brain Res Rev 19: 146–160. 10.1016/0165-0173(94)90007-8 CASPubMedWeb of Science®Google Scholar Brunjes PC, Armstrong AM. 1996. Apoptosis in the rostral migratory stream of the developing rat. Brain Res Dev Brain Res 92: 219–222. 10.1016/0165-3806(96)00006-5 CASPubMedWeb of Science®Google Scholar Brunjes PC, Frazier LL. 1986. Maturation and plasticity in the olfactory system of vertebrates. Brain Res 396: 1–45. 10.1016/0165-0173(86)90008-1 CASPubMedWeb of Science®Google Scholar Burek MJ, Oppenheim RW. 1996. Programmed cell death in the developing nervous system. Brain Pathol 6: 427–446. 10.1111/j.1750-3639.1996.tb00874.x CASPubMedWeb of Science®Google Scholar Chiu K, Greer CA. 1996. Immunocytochemical analyses of astrocyte development in the olfactory bulb. Brain Res Dev Brain Res 95: 28–37. 10.1016/0165-3806(96)00055-7 CASPubMedWeb of Science®Google Scholar Collins JA, Schandi CA, Young KK, Vesely J, Willingham MC. 1997. Major DNA fragmentation is a late event in apoptosis. J Histochem Cytochem 45: 923–934. 10.1177/002215549704500702 CASPubMedWeb of Science®Google Scholar Courtney MJ, Akerman KEO, Coffey ET. 1997. Neurotrophins protect cultured cerebellar granule neurons against the early phase of cell death by a two-component mechanism. J Neurosci 17: 4201–4211. CASPubMedWeb of Science®Google Scholar Cummings DM, Henning HE, Brunjes PC. 1997a. Olfactory bulb recovery after early sensory deprivation. J Neurosci 17: 7433–7440. 10.1523/JNEUROSCI.17-19-07433.1997 CASPubMedWeb of Science®Google Scholar Cummings DM, Knab BR, Brunjes PC. 1997b. Effects of unilateral olfactory deprivation in the developing opossum, Monodelphis domestica. J Neurobiol 33: 429–438. 10.1002/(SICI)1097-4695(199710)33:4<429::AID-NEU7>3.0.CO;2-C CASPubMedWeb of Science®Google Scholar de Torres C, Munell F, Ferrer I, Reventos J, Macaya A. 1997. Identification of necrotic cell death by the TUNEL assay in the hypoxic-ischemic neonatal rat brain. Neurosci Lett 230: 1–4. 10.1016/S0304-3940(97)00445-X CASPubMedWeb of Science®Google Scholar Frazier LL, Brunjes PC. 1988. Unilateral odor deprivation: early postnatal changes in olfactory bulb cell density and number. J Comp Neurol 269: 355–370. 10.1002/cne.902690304 CASPubMedWeb of Science®Google Scholar Frazier-Cierpial LL, Brunjes PC. 1989. Early postnatal cellular proliferation and survival in the olfactory bulb and rostral migratory stream of normal and unilaterally odor-deprived rats. J Comp Neurol 289: 481–492. 10.1002/cne.902890312 CASPubMedWeb of Science®Google Scholar Gavrieli Y, Sherman Y, Ben-Sasson SA. 1992. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119: 493–501. 10.1083/jcb.119.3.493 CASPubMedWeb of Science®Google Scholar Gheusi G, Cremer H, McLean H, Chazal G, Vincent JD, Lledo PM. 2000. Importance of newly generated neurons in the adult olfactory bulb for odor discrimination. Proc Natl Acad Sci USA 97: 1823–1828. 10.1073/pnas.97.4.1823 CASPubMedWeb of Science®Google Scholar Gould E, Woolley CS, McEwen BS. 1991. Naturally occurring cell death in the developing dentate gyrus of the rat. J Comp Neurol 304: 408–418. 10.1002/cne.903040306 CASPubMedWeb of Science®Google Scholar Guthrie KM, Wilson DA, Leon M. 1990. Early unilateral deprivation modifies olfactory bulb function. J Neurosci 10: 3402–3412. CASPubMedWeb of Science®Google Scholar Hinds JW. 1968. Autoradiographic study of histogenesis in the mouse olfactory bulb. I. Time of origin of neurons and neuroglia. J Comp Neurol 134: 287–304. 10.1002/cne.901340304 CASPubMedWeb of Science®Google Scholar Hinds JW, Hinds PL. 1976. Synapse formation in the mouse olfactory bulb. I. Quantitative studies. J Comp Neurol 169: 15–40. 10.1002/cne.901690103 CASPubMedWeb of Science®Google Scholar Kaplan MS, McNelly NA, Hinds JW. 1985. Population dynamics of adult-formed granule neurons of the rat olfactory bulb. J Comp Neurol 239: 117–125. 10.1002/cne.902390110 PubMedWeb of Science®Google Scholar Kishi K. 1987. Golgi studies on the development of granule cells of the rat olfactory bulb with reference to migration in the subependymal layer. J Comp Neurol 258: 112–124. 10.1002/cne.902580109 CASPubMedWeb of Science®Google Scholar Lois C, Alvarez-Buylla A. 1994. Long-distance neuronal migration in the adult mammalian brain. Science 264: 1145–1148. 10.1126/science.8178174 PubMedWeb of Science®Google Scholar Luskin MB. 1993. Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11: 173–189. 10.1016/0896-6273(93)90281-U CASPubMedWeb of Science®Google Scholar Meisami E. 1976. Effects of olfactory deprivation on postnatal growth of the rat olfactory bulb utilizing a new method for production of neonatal unilateral anosmia. Brain Res 107: 437–444. 10.1016/0006-8993(76)90243-2 CASPubMedWeb of Science®Google Scholar Meisami E, Noushinfar E. 1986. Early olfactory deprivation and the mitral cells of the olfactory bulb: a Golgi study. Int J Dev Neurosci 4: 431–444. 10.1016/0736-5748(86)90025-0 PubMedWeb of Science®Google Scholar Meisami E, Safari L. 1981. A quantitative study of the effects of early unilateral olfactory deprivation on the number and distribution of mitral and tufted cells and of glomeruli in the rat olfactory bulb. Brain Res 221: 81–107. 10.1016/0006-8993(81)91065-9 CASPubMedWeb of Science®Google Scholar Morrison RS, Kinoshita Y, Xiang H, Johnson MD, Kuntz C, Ghatan S, Ho JT, Schwartzkroin PA. 1998. Mechanisms of neuronal cell death. Ment Retard Dev Disabil Rev 4: 157–170. 10.1002/(SICI)1098-2779(1998)4:3<157::AID-MRDD3>3.0.CO;2-L Web of Science®Google Scholar Najbauer J, Leon M. 1995. Olfactory experience modulated apoptosis in the developing olfactory bulb. Brain Res 674: 245–251. 10.1016/0006-8993(94)01448-Q CASPubMedWeb of Science®Google Scholar Negoescu A, Guillermet C, Lorimier P, Brambilla E, Labatmoleur F. 1998. Importance of DNA fragmentation in apoptosis with regard to TUNEL specificity. Biomed Pharmacother 52: 252–258. 10.1016/S0753-3322(98)80010-3 CASPubMedWeb of Science®Google Scholar Pettmann B, Henderson CE. 1998. Neuronal cell death. Neuron 20: 633–647. 10.1016/S0896-6273(00)81004-1 CASPubMedWeb of Science®Google Scholar Philpot BD, Foster TC, Brunjes PC. 1997. Mitral/tufted cell activity is attenuated and becomes uncoupled from respiration following naris closure. J Neurobiol 33: 374–386. 10.1002/(SICI)1097-4695(199710)33:4<374::AID-NEU3>3.0.CO;2-7 CASPubMedWeb of Science®Google Scholar Rosselli-Austin L, Altman J. 1979. The postnatal development of the main olfactory bulb of the rat. J Dev Physiol 1: 295–313. CASPubMedGoogle Scholar Shipley MT, Ennis M. 1996. Functional organization of olfactory system. J Neurobiol 30: 123–176. 10.1002/(SICI)1097-4695(199605)30:1<123::AID-NEU11>3.0.CO;2-N CASPubMedWeb of Science®Google Scholar Skeen LC, Due BR, Douglas FE. 1985. Effects of early anosmia on two classes of granule cells in developing mouse olfactory bulbs. Neurosci Lett 54: 301–306. 10.1016/S0304-3940(85)80095-1 CASPubMedWeb of Science®Google Scholar Skeen LC, Due BR, Douglas FE. 1986. Neonatal sensory deprivation reduces tufted cell number in mouse olfactory bulbs. Neurosci Lett 63: 5–10. 10.1016/0304-3940(86)90003-0 CASPubMedWeb of Science®Google Scholar Tanaka M, Marunouchi T. 1998. Immunohistochemical analysis of developmental stage of external granular layer neurons which undergo apoptosis in postnatal rat cerebellum. Neurosci Lett 242: 85–88. 10.1016/S0304-3940(98)00032-9 CASPubMedWeb of Science®Google Scholar Thomaidou D, Mione MC, Cavanagh JFR, Parnavelas JG. 1997. Apoptosis and its relation to the cell cycle in the developing cerebral cortex. J Neurosci 17: 1075–1085. 10.1523/JNEUROSCI.17-03-01075.1997 CASPubMedWeb of Science®Google Scholar Wood KA, Dipasquale B, Youle RJ. 1993. In situ labeling of granule cells for apoptosis-associated DNA fragmentation reveals different mechanisms of cell loss in developing cerebellum. Neuron 11: 621–632. 10.1016/0896-6273(93)90074-2 CASPubMedWeb of Science®Google Scholar Citing Literature Volume431, Issue312 March 2001Pages 311-319 ReferencesRelatedInformation