Skip to main content
SpringerLink
Log in

In human brain ornithine transcarbamylase (OTC) immunoreactivity is strongly expressed in a small number of nitrergic neurons

  • Short Communication
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

There is recent evidence for ornithine transcarbamylase (OTC) expression in adult human brain. We decided to immunocytochemically map OTC throughout brain, and to further characterize OTC-immunopositive neurons. By using double immunolabeling technique for OTC and neuronal nitric oxide synthase (nNOS) OTC protein expression was revealed in a small subset of nitrergic (nNOS) neurons. Since citrulline (the reaction product of OTC) enhances the bioavailability of L-arginine, the substrate of nNOS, it is conceivable that OTC activity supports NO production in nitrergic neurons.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  • Bensemain F, Hot D, Ferreira S, Dumont J, Bombois S, Maurage CA, Huot L, Hermant X, Levillain E, Hubans C, Hansmannel F, Chapuis J, Hauw JJ, Schraen S, Lemoine Y, Buée L, Berr C, Mann D, Pasquier F, Amouyel P, Lambert JC (2009) Evidence for induction of the ornithine transcarbamylase expression in Alzheimer's disease. Mol Psychiatry 14(1):106–116

    Article  CAS  PubMed  Google Scholar 

  • Bernstein HG, Stanarius A, Baumann B, Henning H, Krell D, Danos P, Falkai P, Bogerts B (1998) Nitric oxide synthase-containing neurons in the human hypothalamus: reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics. Neuroscience 83:867–375

    Article  CAS  PubMed  Google Scholar 

  • Bernstein HG, Baumann B, Danos P, Diekmann S, Bogerts B, Gundelfinger ED, Braunewell KH (1999) Regional and cellular distribution of neural visinin-like protein immunoreactivities (VILIP-1 and VILIP-3) in human brain. J Neurocytol 28:655–662

    Article  CAS  PubMed  Google Scholar 

  • Bernstein HG, Tausch A, Wagner R, Steiner J, Seeleke P, Walter M, Dobrowolny H, Bogerts B (2014) Disruption of glutamate-glutamine-GABA cycle significantly impacts on suicidal behaviour: survey of the literature and own findings on glutamine synthetase. CNS Neurol Disord Drug Targets 12(7):900–913

    Article  Google Scholar 

  • Bernstein HG, Jäger K, Dobrowolny H, Steiner J, Keilhoff G, Bogerts B, Laube G (2015) Possible sources and functions of L-homoarginine in the brain: review of the literature and own findings. Amino Acids 7:1729–1740. https://doi.org/10.1007/s00726-015-1960-y.

    Article  Google Scholar 

  • Bertram I, Bernstein HG, Lendeckel U, Bukowska A, Dobrowolny H, Keilhoff G, Kanakis D, Mawrin C, Bielau H, Falkai P, Bogerts B (2007) Immunohistochemical evidence for impaired neuregulin-1 signaling in the prefrontal cortex in schizophrenia and in unipolar depression. Ann N Y Acad Sci 1096:147–156

    Article  CAS  PubMed  Google Scholar 

  • Braissant O (2010) Current concepts in the pathogenesis of urea cycle disorders. Mol Genet Metab 100(Suppl 1):S3–S12. https://doi.org/10.1016/j.ymgme.2010.02.010.

    Article  CAS  PubMed  Google Scholar 

  • Buniatian HC (1971) The urea cycle. In: Metabolic Turnover in the Nervous System (Rappoport DA, Fritz RR, Yamagami S, Herrmann RL et al. eds.) Handbook of Neurochemistry vol. V. Plenum Press New York London, pp. 235.248

  • Butterworth RF (2000) Evidence for forebrain cholinergic neuronal loss in congenital ornithine transcarbamylase deficiency. Metab Brain Dis 15(1):83–91

    CAS  PubMed  Google Scholar 

  • Dumont J, Meroufel D, Bauters C, Hansmannel F, Bensemain F, Cottel D, Hamon M, Lambert JC, Ducimetière P, Amouyel P, Zureik M, Brousseau T (2009) Association of ornithine transcarbamylase gene polymorphisms with hypertension and coronary artery vasomotion. Am J Hypertens 22(9):993–1000. https://doi.org/10.1038/ajh.2009.110.

    Article  CAS  PubMed  Google Scholar 

  • Gropman AL, Shattuck K, Prust MJ, Seltzer RR, Breeden AL, Hailu A, Rigas A, Hussain R, VanMeter J (2013) Altered neural activation in ornithine transcarbamylase deficiency during executive cognition: an fMRI study. Hum Brain Map 34(4):753–761. https://doi.org/10.1002/hbm.21470. 23

    Article  Google Scholar 

  • Hansmannel F, Lendon C, Pasquier F, Dumont J, Hannequin D, Chapuis J, Laumet G, Ayral AM, Galimberti D, Scarpini E, Campion D, Amouyel P, Lambert JC (2009) Is the ornithine transcarbamylase gene a genetic determinant of Alzheimer's disease? Neurosci Lett 449(1):76–80. https://doi.org/10.1016/j.neulet.2008.10.081.

    Article  CAS  PubMed  Google Scholar 

  • Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, van de Lagemaat LN et al (2012) An anatomically comprehensive atlas of the adult human transcriptome. Nature 489:391–399. https://doi.org/10.1038/nature11405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hernández-Rabaza V, Cabrera-Pastor A, Taoro-González L, Malaguarnera M, Agustí A, Llansola M, Felipo V (2016) Hyperammonemia induces glial activation, neuroinflammation and alters neurotransmitter receptors in hippocampus, impairing spatial learning: reversal by sulforaphane. J Neuroinflammation 13:41. https://doi.org/10.1186/s12974-016-0505-y.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hou Y, Hu S, Jia S, Nawaratna G, Che D, Wang F, Bazer FW, Wu G (2016) Whole-body synthesis of L-homoarginine in pigs and rats supplemented with L-arginine. Amino Acids 48(4):993–1001. https://doi.org/10.1007/s00726-015-2145-4.

    Article  CAS  PubMed  Google Scholar 

  • Keilhoff G, Wolf G (2003) Citrulline immunohistochemistry may not necessarily identify nitric oxide synthase activity: the pitfall of peptidylarginine deiminase. Nitric Oxide 8(1):31–38

    Article  CAS  PubMed  Google Scholar 

  • Liang WS, Reiman EM, Valla J, Dunckley T, Beach TG, Grover A et al (2008) Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. Proc Natl Acad Sci U S A 105(11):4441–4446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopes-Marques M, Pereira-Castro I, Amorim A, Azevedo L (2012) Characterization of the human ornithine transcarbamylase 3′ untranslated regulatory region. DNA Cell Biol 31(4):427–433. https://doi.org/10.1089/dna.2011.1391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luiking YC, Hallemeesch MM, van de Poll MC, Dejong CH, de Jonge WJ, Lamers WH, Deutz NE (2008) Reduced citrulline availability by OTC deficiency in mice is related to reduced nitric oxide production. Am J Physiol Endocrinol Metab 295(6):E1315–E1322. https://doi.org/10.1152/ajpendo.00055.2008

    Article  CAS  PubMed  Google Scholar 

  • Martinelli GP, Friedrich VL Jr, Holstein GR (2002) L-citrulline immunostaining identifies nitric oxide production sites within neurons. Neuroscience 114(1):111–122

    Article  CAS  PubMed  Google Scholar 

  • Morris SM Jr (2016) Arginine metabolism revisited. J Nutr 146(12):2579S–2586S

    Article  CAS  PubMed  Google Scholar 

  • Ratnakumari L, Qureshi IA, Butterworth RF, Marescau B, De Deyn PP (1996) Arginine-related guanidino compounds and nitric oxide synthase in the brain of ornithine transcarbamylase deficient spf mutant mouse: effect of metabolic arginine deficiency. Neurosci Lett 215(3):153–156

    Article  CAS  PubMed  Google Scholar 

  • Walker V (2012) Severe hyperammonaemia in adults not explained by liver disease. Ann Clin Biochem 49(Pt 3):214–228. https://doi.org/10.1258/acb.2011.011206

    Article  CAS  PubMed  Google Scholar 

  • Wiesinger H (2001) Arginine metabolism and the synthesis of nitric oxide in the nervous system. Prog Neurobiol 64(4):365–391

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, D-39120, Magdeburg, Germany

    Hans-Gert Bernstein, Hendrik Dobrowolny & Johann Steiner

  2. Institute of Biochemistry and Cell Biology, Medical Faculty, University of Magdeburg, D-39120, Magdeburg, Germany

    Gerburg Keilhoff

Authors
  1. Hans-Gert Bernstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hendrik Dobrowolny
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gerburg Keilhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Johann Steiner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hans-Gert Bernstein.

Ethics declarations

Conflict of interest

Nothing to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bernstein, HG., Dobrowolny, H., Keilhoff, G. et al. In human brain ornithine transcarbamylase (OTC) immunoreactivity is strongly expressed in a small number of nitrergic neurons. Metab Brain Dis 32, 2143–2147 (2017). https://doi.org/10.1007/s11011-017-0105-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-017-0105-2

Keywords

Search

Navigation