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Pharmacopsychiatry 2012; 45(06): 241-243
DOI: 10.1055/s-0032-1301914
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Altered Neurotrophin, Neuropeptide, Cytokines and Nitric Oxide Levels in Autism

M.H.F. S. Tostes
1   NUPICS/NIQUA, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil
,
H. C. Teixeira
2   Department of Parasitology, Microbiology and Immunology, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil
,
W. F. Gattaz
3   Laboratory of Neuroscience, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, SP, Brazil
,
M.A. F. Brandão
1   NUPICS/NIQUA, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil
,
N.R. B. Raposo
1   NUPICS/NIQUA, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil
3   Laboratory of Neuroscience, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, SP, Brazil
› Author Affiliations
Further Information

Publication History

received 04 May 2011
revised 16 January 2012

accepted 16 January 2012

Publication Date:
16 March 2012 (online)

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Abstract

Introduction:

Modifications in neurotrophins, neuropeptides, cytokines and nitric oxide (NO) levels in autism may represent different biological aspects of the disease. In the present study we investigate simultaneously all these variables as an attempt to clarify their interrelationships in autism.

Methods:

Plasma levels of vasoactive intestinal peptide (VIP), neurotrophin-3 (NT-3), cytokines and nitric oxide (NO) were determined in children with DSM-IV autistic disorder (n=24) and in age- and gender-matched healthy controls (n=24). VIP, NT-3, IFN-γ and IL-1β levels were measured by ELISA, TNF-α, IL-10, IL-6, IL-4, IL-2 were evaluated by flow cytometry, and NO by Griess reaction.

Results:

Plasma levels of VIP, IFN-γ and NO were significantly higher and NT-3 plasma levels were significantly lower in children with autism, compared to the healthy subjects. In children with autism there was a positive correlation between plasma levels of NO and IFN-γ.

Discussion:

Our results indicate the presence of altered levels of neurotrophin and neuropeptide in infantile autism and provide additional evidence that higher levels of IFN-γ may be associated with increased oxidative stress in autism.

Key words

autism - children - VIP - NT-3 - cytokines - nitric oxide
 

  • References

  • 1 Chauhan A, Chauhan V. Oxidative stress in autism. Pathophysiology 2006; 13: 171-181
    CrossrefPubMedSearch in Google Scholar
  • 2 Sweeten TL, Posey DJ, Shankar S et al. High nitric oxide production in autistic disorder: a possible role for interferon-gamma. Biol Psychiatry 2004; 55: 434-437
    CrossrefPubMedSearch in Google Scholar
  • 3 Lonart G, Wang J, Johnson KM. Nitric oxide induces neurotransmitter release from hippocampal slices. Eur J Pharmacol 1992; 220: 271-272
    CrossrefPubMedSearch in Google Scholar
  • 4 Hindley S, Juurlink BH, Gysbers JW et al. Nitric oxide donors enhance neurotrophin-induced neurite outgrowth through a cGMP-dependent mechanism. J Neurosci Res 1997; 47: 427-439
    CrossrefPubMedSearch in Google Scholar
  • 5 Truman JW, De Vente J, Ball EE. Nitric oxide-sensitive guanylate cyclase activity is associated with the maturational phase of neuronal development in insects. Development 1996; 122: 3949-3958
    PubMedSearch in Google Scholar
  • 6 Hölscher C, Rose SP. An inhibitor of nitric oxide synthesis prevents memory formation in the chick. Neurosci Lett 1992; 145: 165-167
    CrossrefPubMedSearch in Google Scholar
  • 7 Brenneman DE, Eiden LE. Vasoactive Intestinal Peptide and electrical activity influence neuronal survival. Proc Natl Acad Sci USA 1986; 83: 1159-1162
    CrossrefPubMedSearch in Google Scholar
  • 8 Brenneman DE, Gozes I. A femtomolar-acting neuroprotective peptide. J Clin Invest 1996; 97: 2299-2307
    CrossrefPubMedSearch in Google Scholar
  • 9 Nelson KB, Grether JK, Croen LA et al. Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation. Ann Neurol 2001; 49: 597-606
    CrossrefPubMedSearch in Google Scholar
  • 10 Castrén E, Võikar V, Rantamäki T. Role of neurotrophic factors in depression. Curr Opin Pharmacol 2007; 7: 18-21
    CrossrefPubMedSearch in Google Scholar
  • 11 Segal RA. Selectivity in neurotrophin signaling: theme and variations. Ann Rev Neurosci 2003; 26: 299-330
    CrossrefPubMedSearch in Google Scholar
  • 12 Kovalchuk Y, Holthoff K, Konnerth A. Neurotrophin action on a rapid timescale. Curr Opin Neurobiol 2004; 14: 558-563
    CrossrefPubMedSearch in Google Scholar
  • 13 WMA  −  World Medical Association Declaration of Helsinki Edinburgh: 52nd General Assembly  −  WMA 2000
    PubMed
  • 14 APA – American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR. Washington: American Psychiatric Association; 1994
    Search in Google Scholar
  • 15 Green LC, Wagner DA, Glogowsk J et al. Analysis of nitrate, nitrite and nitrate in biological fluids. Anal Biochem 1982; 126: 131-138
    CrossrefPubMedSearch in Google Scholar
  • 16 Nelson PG, Kuddo T, Song EY et al. Selected neurotrophins, neuropeptides, and cytokines: developmental trajectory and concentrations in neonatal blood of children with autism or Down syndrome. Int J Devel Neurosci 2006; 24: 73-80
    CrossrefPubMedSearch in Google Scholar
  • 17 Sajdel-Sulkowska E, Ming X, Koibuchi N. Increase in cerebellar neurotrophin-3 and oxidative stress markers in autism. Cerebellum 2009; 8: 366-372
    CrossrefPubMedSearch in Google Scholar
  • 18 Pan W, Banks WA, Fasold MB et al. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 1998; 37: 1553-1561
    CrossrefPubMedSearch in Google Scholar
  • 19 Sajdel-Sulkowska E. Oxidative stress and neurotrophin signaling in autism. In: Chauhan A, Chauhan V, Brown T. (eds.). Autism: Oxidative stress, Inflammation and Immune abnormalities (47–60). New York: CRC Press; 2010
    Search in Google Scholar
  • 20 Sherrard RM, Bower AJ. Climbing fibre development: do neurotrophins have a part to play?. Cerebellum 2002; 1: 262-275
    PubMedSearch in Google Scholar
  • 21 Blondel O, Collin C, McCarran B et al. A glia-derived signal regulating neuronal differentiation. J Neurosci 2000; 2: 8012-8020
    PubMedSearch in Google Scholar
  • 22 Fernandes BS, Gama CS, Walz JC et al. Increased neurotrophin-3 in drug-free subjects with bipolar disorder during manic and depressive episodes. J Psychiatry Res 2010; 44: 561-565
    CrossrefPubMedSearch in Google Scholar
  • 23 Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry 2006; 59: 1116-1127
    CrossrefPubMedSearch in Google Scholar
  • 24 Kato A, Fukuzawa Y, Ozawa I et al. Activation of ERK cascade promotes accumulation of Vesi1S/Homer-1a immunoreactivity at synapses. Mol Brain Res 2003; 118: 33-34
    CrossrefPubMedSearch in Google Scholar
  • 25 Agerman K, Ernfors P. Differential influence of BDNF and NT3 on the expression of calcium binding proteins and neuropeptide Y in vivo. NeuroReport 2003; 14: 2183-2187
    CrossrefPubMedSearch in Google Scholar
  • 26 Schutte A, Yan Q, Mestres P et al. The endogenous survival promotion of axotomized rat corticospinal neurons by brain-derived neurotrophic factor is mediated via paracrine, rather than autocrine mechanisms. Neurosci Lett 2000; 290: 185-188
    CrossrefPubMedSearch in Google Scholar
  • 27 Giehl KM, Röhrig S, Bonatz H et al. Endogenous brain-derived neurotrophic factor and neurotrophin-3 antagonistically regulate survival of axotomized corticospinal neurons in vivo. J Neurosci 2001; 21: 3492-3502
    PubMedSearch in Google Scholar
  • 28 Nelson PG, McCune SK, Ades AM et al. Glial-neurotrophic mechanisms in Down syndrome. J Neural Transm 2001; 61 (Suppl) 85-94
    PubMedSearch in Google Scholar
  • 29 Brenenman DE, Hauser J, Phillips TM et al. Vasoactive Intestinal Peptide: link between electrical activity and glia-mediated neurotrophism. Ann N Y Acad Sci 1999; 897: 17-26
    CrossrefPubMedSearch in Google Scholar
  • 30 Tran MT, Ritchie MH, Lausch RN et al. Calcitonin gene-related peptide induces IL-8 synthesis in corneal epithelial cells. J Immunol 2000; 164: 4307-4312
    PubMedSearch in Google Scholar
  • 31 Delgado M, Ganea D. Vasoactive intestinal peptide inhibits IL-8 production in human monocytes by down regulation nuclear factor kappa B-dependent transcriptional activity. Biochem Biophys Res Commun 2003; 302: 275-283
    CrossrefPubMedSearch in Google Scholar
  • 32 Croonenberghs J, Bosmans E, Deboutte D et al. Activation of the inflammatory response system in autism. Neuropsychobiology 2002; 45: 1-6
    PubMedSearch in Google Scholar
  • 33 Jyonouchi H, Sun S. Proinflammatory and regulatory cytokine production associated with innate and adaptative immune responses in children with autism spectrum disorders and developmental regression. J Neuroimmunol 2001; 120: 170-179
    CrossrefPubMedSearch in Google Scholar
  • 34 Zoroğlu SS, Yürekli M, Meram I et al. Pathophysiological role of nitric oxide and adrenomedullin in autism. Cell Biochem Funct 2003; 21: 55-60
    CrossrefPubMedSearch in Google Scholar