Molecular Neurobiology

, Volume 47, Issue 1, pp 1–8 | Cite as

Expression of Myostatin in Neural Cells of the Olfactory System

  • Shunsuke Iwasaki
  • Masato Miyake
  • Hitoshi Watanabe
  • Eri Kitagawa
  • Kouichi Watanabe
  • Shyuichi Ohwada
  • Haruki Kitazawa
  • Michael T. Rose
  • Hisashi AsoEmail author


Recent studies show that myostatin mRNA expression is found in some regions of the brain. However, the functional significance of this is currently unknown. We therefore investigated myostatin expression and function in the brain. In this study, we used immunohistochemistry, in situ hybridization, and RT-PCR analysis to reveal that myostatin is expressed in the mitral cells in the olfactory bulb (OB) and in neurons in the olfactory cortex (OC). Using 3D reconstruction, mitral cells positive for myostatin were positioned in the lateral and ventral regions of the OB. In contrast, myostatin-positive mitral cells were detected in mice at 2 weeks of age, but not on days 0 and 7 after birth. Activin receptor IIB, a myostatin receptor, was expressed in the OB, OC, hippocampus, and paraventricular thalamic nucleus. Moreover, c-Fos immunostaining in granule cells in the OB was augmented after intracerebroventricular injection of myostatin. These findings suggest that myostatin is localized in specific cells associated with the olfactory system of the brain and may act as a key inhibitor in cell and/or signal development of the olfactory system.


Myostatin Olfactory system Brain Intracerebroventricular injection Neurogenesis 



We acknowledge the late Prof. Takahiro Yamaguchi for helpful comments. This study was supported by a Grant-in-Aid for Scientific Research (A) (No. 17208024) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and also a Research project for utilizing advanced technologies in agriculture, forestry, and fisheries (No. 1523) from the Ministry of Agriculture, Forestry and Fisheries, Japan.


  1. 1.
    McPherron AC, Lawler AM, Lee SJ (1997) Regulation of skeletal muscle mass in mice by a new TGF-β superfamily member. Nature 234:83–89CrossRefGoogle Scholar
  2. 2.
    Szabo G, Dallmann G, Muller G, Patthy L, Soller M, Varga L (1998) A deletion in the myostatin gene causes the compact (Cmpt) hypermuscular mutation in mice. Mamm Genome 9:671–672PubMedCrossRefGoogle Scholar
  3. 3.
    Zhu J, Hadhazy M, Wehling M, Tidball G, McNally EM (2000) Dominant negative myostatin produces hypertrophy without hyperplasia in muscle. FEBS Lett 474:71–75PubMedCrossRefGoogle Scholar
  4. 4.
    Grobet L, Royo LJ, Poncelet D, Pirottin D, Brouwers B, Riquet J, Schoeberlein A, Dunner S, Menissier F, Massabanda J, Fries R, Hanset R, Georges M (1997) A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nat Genet 17:71–74PubMedCrossRefGoogle Scholar
  5. 5.
    Kambadur R, Sharma M, Smith TPL, Bass JJ (1997) Mutations in myostatin (GDF8) in double-muscled Belgian Blue and Piedmontese cattle. Genome Res 7:910–915PubMedGoogle Scholar
  6. 6.
    McPherron AC, Lee SJ (1997) Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci USA 94:12457–12461PubMedCrossRefGoogle Scholar
  7. 7.
    Karim L, Coppieters W, Grobet L, Valentini A, Georges M (2000) Convenient genotyping of six myostatin mutations causing double-muscling in cattle using a multiplex oligonucleotide ligation assay. Anim Genet 31:396–399PubMedCrossRefGoogle Scholar
  8. 8.
    Anderson SB, Goldberg AL, Whitman M (2008) Identification of a novel pool of extracellular pro-myostatin in skeletal muscle. J Biol Chem 283:7027–7035PubMedCrossRefGoogle Scholar
  9. 9.
    Manickam R, Pena RN, Whitelaw CBA (2008) Mammary gland differentiation inversely correlates with GDF-8 expression. Mol Reprod Dev 75:1783–1788PubMedCrossRefGoogle Scholar
  10. 10.
    Sharma M, Kambadur R, Matthews KG, Somers WG, Devlin GP, Conaglen JV, Fowke PJ, Bass JJ (1999) Myostatin, a transforming growth factor-β superfamily member, is expressed in heart muscle and is upregulated in cardiomyocytes after infarct. J Cell Physiol 180:1–9PubMedCrossRefGoogle Scholar
  11. 11.
    Rodgers B, Garikipati DK (2008) Clinical, agricultural, and evolutionary biology of myostatin: a comparative review. Endocr Rev 29:513–534PubMedCrossRefGoogle Scholar
  12. 12.
    Ida T, Mori K, Miyazato M, Egi Y, Abe S, Nakahara K, Nishihara M, Kangawa K, Murakami N (2005) Neuromedin S is a novel anorexigenic hormone. Endocrinology 146:4217–4223PubMedCrossRefGoogle Scholar
  13. 13.
    Wu HH, Ivkovic S, Murray RC, Jaramillo S, Lyons KM, Johnson JE, Calof AL (2003) Autoregulation of neurogenesis by GDF11. Neuron 37:197–207PubMedCrossRefGoogle Scholar
  14. 14.
    McPherron AC (2010) Metabolic functions of myostatin and GDF11. Immunol Endocr Metab Agents Med Chem 10:217–231PubMedCrossRefGoogle Scholar
  15. 15.
    Sato T, Hirono J, Hamana H, Ishikawa T, Shimizu A, Takashima I, Kajiwara R, Iijima T (2008) Architecture of odor information processing in the olfactory system. Anat Sci Int 83:195–206PubMedCrossRefGoogle Scholar
  16. 16.
    Malnic B, Hirono J, Sato T, Buck LB (1999) Combinatorial receptor codes for odors. Cell 96:713–723PubMedCrossRefGoogle Scholar
  17. 17.
    Mori K, Takahashi YK, Igarashi KM, Yamaguchi M (2006) Maps of odorant molecular features in the mammalian olfactory bulb. Physiol Rev 86:409–433PubMedCrossRefGoogle Scholar
  18. 18.
    Kobayakawa K, Kobayakawa R, Matsumoto H, Oka Y, Imai T, Ikawa M, Okabe M, Ikeda T, Itohara S, Kikusui T, Mori K, Sakano H (2007) Innate versus learned odour processing in the mouse olfactory bulb. Nature 450:503–508PubMedCrossRefGoogle Scholar
  19. 19.
    Cameron VA, Nishimura E, Mathews LS, Lewis KA, Sawchenko PE, Vale WW (1994) Hybridization histochemical localization of activin receptor subtypes in rat brain, pituitary, ovary, and testis. Endocrinology 134:799–808PubMedCrossRefGoogle Scholar
  20. 20.
    Ageta H, Murayama A, Migishima R, Kida S, Tsuchida K, Yokoyama M, Inokuchi K (2008) Activin in the brain modulates anxiety-related behavior and adult neurogenesis. PLoS One 3:e1869PubMedCrossRefGoogle Scholar
  21. 21.
    Thomas M, Langley B, Berry C, Sharma M, Kirk S, Bass J, Kambadur R (2000) Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation. J Biol Chem 275:40235–40243PubMedCrossRefGoogle Scholar
  22. 22.
    Langley B, Thomas M, Bishop A, Sharma M, Gilmour S, Kambadur R (2002) Myostatin inhibits myoblast differentiation by down-regulating MyoD expression. J Biol Chem 277:49831–49840PubMedCrossRefGoogle Scholar
  23. 23.
    Yokoi M, Mori K, Nakanishi S (1995) Refinement of odor molecule tuning by dendrodendritic synaptic inhibition in the olfactory bulb. Proc Natl Acad Sci USA 92:3371–3375PubMedCrossRefGoogle Scholar
  24. 24.
    Blanchart A, De Carlos JA, López-Mascaraque L (2006) Time frame of mitral cell development in the mice olfactory bulb. J Comp Neurol 496:529–543PubMedCrossRefGoogle Scholar
  25. 25.
    Wilson DA, Leon M (1986) Early appearance of inhibition in the neonatal rat olfactory bulb. Brain Res 391:289–292PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Shunsuke Iwasaki
    • 1
  • Masato Miyake
    • 1
  • Hitoshi Watanabe
    • 1
  • Eri Kitagawa
    • 1
  • Kouichi Watanabe
    • 1
  • Shyuichi Ohwada
    • 1
  • Haruki Kitazawa
    • 2
  • Michael T. Rose
    • 3
  • Hisashi Aso
    • 1
    Email author
  1. 1.Laboratory of Functional Morphology, Department of Animal Biology, Graduate School of Agricultural ScienceTohoku UniversitySendaiJapan
  2. 2.Food Immunology Group, Laboratory of Animal Products Chemistry Graduate School of Agricultural ScienceTohoku UniversitySendaiJapan
  3. 3.Institute of Biological, Environmental and Rural SciencesAberystwyth UniversityCeredigionUK

Personalised recommendations