Decreased Expression of PTEN in Olfactory Bulb of Rat Pub after Naris Closure

  • Cho, Jae-Young (Department of Pharmacology, College of Medicine, Medical Science Research Institute, Kangwon National University) ;
  • Lee, Sang-Hyun (Department of Pharmacology, College of Medicine, Medical Science Research Institute, Kangwon National University) ;
  • Lee, Geon-Hee (Department of Pharmacology, College of Medicine, Medical Science Research Institute, Kangwon National University) ;
  • Chun, Wan-Joo (Department of Pharmacology, College of Medicine, Medical Science Research Institute, Kangwon National University) ;
  • Park, Yee-Tae (Department of Neuroscience, Medicine Science Research Institute, Kangwon National University) ;
  • Lim, So-Young (Department of Anesthesiology, College of Medicine, Hallym University) ;
  • Kim, Sung-Soo (Department of Pharmacology, College of Medicine and Department of Neuroscience, Medical Science Research Institute, Kangwon National University)
  • Published : 2004.02.21


PTEN (phosphatase and tensin homolog) is a dual specific phosphatase antagonizing phosphoinositide 3-kinase activity, and has first been cloned as a tumor suppressor for glioma. Although the role of PTEN as a tumor suppressor has been well studied, little is known about signaling mechanisms regulating expression and/or activity of PTEN in the central nervous system. In this study, we investigated whether PTEN expression is regulated by sensory deprivation. P5 rat pups were unilaterally naris-closed, and olfactory bulbs were immunohistochemically analyzed with PTEN antibody at the $7^{th}$ day after naris closure. PTEN immunoreactivity was found to be down-regulated in both glomerular, external plexiform and subependymal cell layers, suggesting that odor deprivation signals down-regulate expression of PTEN in the olfactory bulb. To the best of our knowledge, this is the first report to suggest that PTEN expression is regulated by sensory deprivation signals in neonatal rats.


  1. Baker H, Farbman AI. Olfactory afferent regulation of the dopamine phenotype in the fetal rat olfactory system. Neuroscience 52: 115-134, 1993
  2. Cummings DM, Brunjes PC. The effects of variable periods of functional deprivation on olfactory bulb development in rats. Exp Neurol 148: 360-366, 1997
  3. Frazier LL, Brunjes PC. Unilateral odor deprivation: early postnatal changes in olfactory bulb cell density and number. J Comp Neurol 269: 355-370, 1988
  4. Johnson BA, Woo CC, Ninomiya-Tsuboi K, Leon M. Synaptophysin- like immunoreactivity in the rat olfactory bulb during postnatal development and after restricted early olfactory experience. Brain Res Dev Brain Res 92: 24-30, 1996
  5. Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci 114: 2375- 2382, 2001
  6. Eng C. Role of PTEN, a lipid phosphatase upstream effector of protein kinase B, in epithelial thyroid carcinogenesis. Ann N Y Acad Sci 968: 213-221, 2002
  7. Zhang J, Choi Y, Mavromatis B, Lichtenstein A, Li W. Preferential killing of PTEN-null myelomas by PI3K inhibitors through Akt pathway. Oncogene 22: 6289-6295, 2003
  8. Gu J, Tamura M, Pankov R, Danen EH, Takino T, Matsumoto K, Yamada KM. Shc and FAK differentially regulate cell motility and directionality modulated by PTEN. J Cell Biol 146: 389- 403, 1999
  9. Cho J, Lee SH, Seo JH, Kim HS, Ahn JG, Kim SS, Yim SV, Song DK, Cho SS. Increased expression of phosphatase and tensin homolog in reactive astrogliosis following intracerebroventricular kainic acid injection in mouse hippocampus. Neurosci Lett 334: 131-134, 2002
  10. Lois C, Alvarez-Buylla A. Long-distance neuronal migration in the adult mammalian brain. Science 264: 1145-1148, 1994
  11. Weiler E, Farbman AI. Proliferation decrease in the olfactory epithelium during postnatal development. Ann N Y Acad Sci 855: 230-234, 1998
  12. Li L, Liu F, Ross AH. PTEN regulation of neural development and CNS stem cells. J Cell Biochem 88: 24-28, 2003
  13. Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, Ruland J, Penninger JM, Siderovski DP, Mak TW. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95: 29-39, 1998
  14. Di Cristofano A, Pandolfi PP. The multiple roles of PTEN in tumor suppression. Cell 100: 387-390, 2000
  15. Brunjes PC, Smith-Crafts LK, McCarty R. Unilateral odor deprivation: effects on the development of olfactory bulb catecholamines and behavior. Brain Res 354: 1-6, 1985
  16. Li L, Liu F, Salmonsen RA, Turner TK, Litofsky NS, Di Cristofano A, Pandolfi PP, Jones SN, Recht LD, Ross AH. PTEN in neural precursor cells: regulation of migration, apoptosis, and proliferation. Mol Cell Neurosci 20: 21-29, 2002
  17. Nagatsu T, Levitt M, Udenfriend S. Conversion of L-tyrosine to 3,4-dihydroxyphenylalanine by cell-free preparations of brain and sympathetically innervated tissues. Biochem Biophys Res Commun 14: 543-549, 1964
  18. Stambolic V, MacPherson D, Sas D, Lin Y, Snow B, Jang Y, Benchimol S, Mak TW. Regulation of PTEN transcription by p53. Mol Cell 8: 317-325, 2001
  19. Besson A, Robbins SM, Yong VW. PTEN/MMAC1/TEP1 in signal transduction and tumorigenesis. Eur J Biochem 263: 605-611, 1999
  20. Benson TE, Ryugo DK, Hinds JW. Effects of sensory deprivation on the developing mouse olfactory system: a light and electron microscopic, morphometric analysis. J Neurosci 4: 638-653, 1984
  21. Lachyankar MB, Sultana N, Schonhoff CM, Mitra P, Poluha W, Lambert S, Quesenberry PJ, Litofsky NS, Recht LD, Nabi R. A role for nuclear PTEN in neuronal differentiation. J Neurosci 20: 1404-1413, 2000
  22. Maehama T, Dixon JE. PTEN: a tumour suppressor that functions as a phospholipid phosphatase. Trends Cell Biol 9: 125-128, 1999
  23. Weiler E, Farbman AI. Proliferation in the rat olfactory epithelium: age-dependent changes. J Neurosci 17: 3610-3622, 1997
  24. Tamura M, Gu J, Danen EH, Takino T, Miyamoto S, Yamada KM. PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3- kinase/Akt cell survival pathway. J Biol Chem 274: 20693- 20703, 1999