Skip to main content

Advertisement

SpringerLink
Log in

Comparative efficacy of alpha-linolenic acid and gamma-linolenic acid to attenuate valproic acid-induced autism-like features

  • Original Article
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

The present study was undertaken to elucidate the effect of alpha-linolenic acid (ALA, 18:3, ω-3) and gamma-linolenic acid (GLA, 18:3, ω-6) on experimental autism features induced by early prenatal exposure to valproic acid (VPA) in albino wistar pups. The pups were scrutinized on the accounts of behavioral, biochemical, and inflammatory markers, and the results suggested that the GLA can impart significant protection in comparison to ALA against VPA-induced autism features. When scrutinized histopathologically, the cerebellum of the GLA-treated animals was evident for more marked protection toward neuronal degeneration and neuronal loss in comparison to ALA. Concomitant administration of ALA and GLA with VPA demonstrated a marked cutdown in the Pgp 9.5 expression with GLA having more pronounced effect. Henceforth, it can be concluded that ALA and GLA can impart favorable protection against the VPA-induced autism-like features with GLA having pronounced effect.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Al-Gadani Y, El-Ansary A, Attas O, Al-Ayadhi L (2009) Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children. Clin Biochem 42:1032–1040

    Article  CAS  PubMed  Google Scholar 

  2. Altman J, Sudarshan K (1975) Postnatal development of locomotion in the laboratory rat. Anim Behav 23:896–920

    Article  CAS  PubMed  Google Scholar 

  3. Anand R, Kaithwas G (2014) Anti-inflammatory potential of alpha-linolenic acid mediated through selective COX inhibition: computational and experimental data. Inflammation 37:1297–1306

    Article  CAS  PubMed  Google Scholar 

  4. Bambini-Junior V, Rodrigues L, Behr GA, Moreira JCF, Riesgo R, Gottfried C (2011) Animal model of autism induced by prenatal exposure to valproate: behavioral changes and liver parameters. Brain Res 1408:8–16

    Article  CAS  PubMed  Google Scholar 

  5. Bauman M, Kemper TL (1985) Histoanatomic observations of the brain in early infantile autism. Neurology 35:866–866

    Article  CAS  PubMed  Google Scholar 

  6. Bauman ML, Kemper TL (2005) Neuroanatomic observations of the brain in autism: a review and future directions. Int J Dev Neurosci 23:183–187

    Article  PubMed  Google Scholar 

  7. Belch JJ, Hill A (2000) Evening primrose oil and borage oil in rheumatologic conditions. Am J Clin Nutr 71:352s–356s

    CAS  PubMed  Google Scholar 

  8. Belur B, Kandaswamy N, Mukherjee K (1990) Laboratory techniques in histopathology. Medical laboratory technology

  9. Bent S, Bertoglio K, Ashwood P, Bostrom A, Hendren RL (2011) A pilot randomized controlled trial of omega-3 fatty acids for autism spectrum disorder. J Autism Dev Disord 41:545–554

    Article  PubMed  Google Scholar 

  10. Bhosale UA, Yegnanarayan R, Pophale PD, Zambare MR, Somani RS (2011) Study of central nervous system depressant and behavioral activity of an ethanol extract of Achyranthes aspera (Agadha) in different animal models. International Journal of Applied and Basic Medical Research 1:104

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bilguvar K, Tyagi NK, Ozkara C, Tuysuz B, Bakircioglu M, Choi M, Delil S, Caglayan AO, Baranoski JF, Erturk O (2013) Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration. Proc Natl Acad Sci 110:3489–3494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bourre J, Dumont O, Piciotti M, Clement M, Chaudiere J, Bonneil M, Nalbone G, Lafont H, Pascal G, Durand G (1991) Essentiality of ω3 fatty acids for brain structure and function1. In: health effects of omega 3 polyunsaturated fatty acids in seafoods. Karger Publishers, pp 103–117

  13. Covington MB (2004) Omega-3 fatty acids. Atlantic 1:2.0

    Google Scholar 

  14. Crane FL, Low H, Sun IL (2012) Evidence for a relation between plasma membrane coenzyme Q and autism. Frontiers in bioscience (Elite edition) 5:1011–1016

    Google Scholar 

  15. Croen LA, Grether JK, Hoogstrate J, Selvin S (2002) The changing prevalence of autism in California. J Autism Dev Disord 32:207–215

    Article  PubMed  Google Scholar 

  16. Cullen L, Kelly L, Connor SO, Fitzgerald DJ (1998) Selective cyclooxygenase-2 inhibition by nimesulide in man. J Pharmacol Exp Ther 287:578–582

    CAS  PubMed  Google Scholar 

  17. Daynes RA, Jones DC (2002) Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol 2:748–759

    Article  CAS  PubMed  Google Scholar 

  18. Depino AM (2013) Peripheral and central inflammation in autism spectrum disorders. Mol Cell Neurosci 53:69–76

    Article  CAS  PubMed  Google Scholar 

  19. El-Ansary AK, Bacha AGB, Al-Ayadhi LY (2011) Impaired plasma phospholipids and relative amounts of essential polyunsaturated fatty acids in autistic patients from Saudi Arabia. Lipids Health Dis 10:1

    Article  Google Scholar 

  20. Elsabbagh M, Divan G, Koh YJ, Kim YS, Kauchali S, Marcín C, Montiel-Nava C, Patel V, Paula CS, Wang C (2012) Global prevalence of autism and other pervasive developmental disorders. Autism Res 5:160–179

    Article  PubMed  PubMed Central  Google Scholar 

  21. Folch J, Lees M, Sloane-Stanley G (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509

    CAS  PubMed  Google Scholar 

  22. Gong B, Cao Z, Zheng P, Vitolo OV, Liu S, Staniszewski A, Moolman D, Zhang H, Shelanski M, Arancio O (2006) Ubiquitin hydrolase Uch-L1 rescues β-amyloid-induced decreases in synaptic function and contextual memory. Cell 126:775–788

    Article  CAS  PubMed  Google Scholar 

  23. Haas H, Schauenstein K (2001) Immunity, hormones, and the brain. Allergy 56:470–477

    Article  CAS  PubMed  Google Scholar 

  24. Kaithwas G, Majumdar DK (2012) In vitro antioxidant and in vivo antidiabetic, antihyperlipidemic activity of linseed oil against streptozotocin-induced toxicity in albino rats. Eur J Lipid Sci Technol 114:1237–1245

    Article  CAS  Google Scholar 

  25. Kaithwas G, Dubey K, Bhatia D, Sharma AD, Pillai K (2007) Reversal of sodium nitrite induced impairment of spontaneous alteration by Aloe vera gel: involvement of cholinergic system. Pharmacologyonline 3:428–437

    Google Scholar 

  26. Kaithwas G, Mukerjee A, Kumar P, Majumdar DK (2011a) Linum usitatissimum (linseed/flaxseed) fixed oil: antimicrobial activity and efficacy in bovine mastitis. Inflammopharmacology 19:45–52

    Article  CAS  PubMed  Google Scholar 

  27. Kaithwas G, Mukherjee A, Chaurasia A, Majumdar DK (2011b) Antiinflammatory, analgesic and antipyretic activities of Linum usitatissimum L. (flaxseed/linseed) fixed oil. Indian J Exp Biol 49(12):932–938

    CAS  PubMed  Google Scholar 

  28. Kapoor R, Huang Y-S (2006) Gamma linolenic acid: an antiinflammatory omega-6 fatty acid. Curr Pharm Biotechnol 7:531–534

    Article  CAS  PubMed  Google Scholar 

  29. Karvat G, Kimchi T (2014) Acetylcholine elevation relieves cognitive rigidity and social deficiency in a mouse model of autism. Neuropsychopharmacology 39:831–840

    Article  CAS  PubMed  Google Scholar 

  30. Kern JK, Geier DA, Sykes LK, Geier MR (2013) Evidence of neurodegeneration in autism spectrum disorder. Translational neurodegeneration 2:1

    Article  Google Scholar 

  31. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  CAS  PubMed  Google Scholar 

  32. Lu W, Zhao X, Xu Z, Dong N, Zou S, Shen X, Huang J (2013) Development of a new colorimetric assay for lipoxygenase activity. Anal Biochem 441:162–168

    Article  CAS  PubMed  Google Scholar 

  33. Lyall K, Munger KL, O'Reilly ÉJ, Santangelo SL, Ascherio A (2013) Maternal dietary fat intake in association with autism spectrum disorders. Am J Epidemiol :kws433

  34. Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, Shago M, Moessner R, Pinto D, Ren Y (2008) Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 82:477–488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Meiri G, Bichovsky Y, Belmaker R (2009) Omega 3 fatty acid treatment in autism. Journal of child and adolescent psychopharmacology 19:449–451

    Article  PubMed  Google Scholar 

  36. Mosconi MW, Wang Z, Schmitt LM, Tsai P, Sweeney JA (2015) The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders. Front Neurosci 9

  37. Nader R, Oberlander TF, Chambers CT, Craig KD (2004) Expression of pain in children with autism. Clin J Pain 20:88–97

    Article  PubMed  Google Scholar 

  38. Olexová L, Senko T, Štefánik P, Talarovičová A, Kršková L (2013) Habituation of exploratory behaviour in VPA rats: animal model of autism. Interdiscip Toxicol 6:222–227

    Article  PubMed  PubMed Central  Google Scholar 

  39. Poling JS, Frye RE, Shoffner J, Zimmerman AW (2006) Developmental regression and mitochondrial dysfunction in a child with autism. J Child Neurol 21:170–172

    Article  PubMed  PubMed Central  Google Scholar 

  40. Raj P, Singh M, Rawat JK, Gautam S, Saraf SA, Kaithwas G (2014) Effect of enteral administration of α-linolenic acid and linoleic acid against methotrexate induced intestinal toxicity in albino rats. RSC Adv 4:60397–60403

    Article  CAS  Google Scholar 

  41. Reznick AZ, Packer L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 233:357–363

    Article  CAS  PubMed  Google Scholar 

  42. Riendeau D, Percival M, Brideau C, Charleson S, Dube D, Ethier D, Falgueyret J-P, Friesen R, Gordon R, Greig G (2001) Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2. J Pharmacol Exp Ther 296:558–566

    CAS  PubMed  Google Scholar 

  43. Rolf L, Haarmann F, Grotemeyer KH, Kehrer H (1993) Serotonin and amino acid content in platelets of autistic children. Acta Psychiatr Scand 87:312–316

    Article  CAS  PubMed  Google Scholar 

  44. Rose S, Frye RE, Slattery J, Wynne R, Tippett M, Pavliv O, Melnyk S, James SJ (2014) Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort. PLoS One 9:e85436

    Article  PubMed  PubMed Central  Google Scholar 

  45. Rossi R, Tsikas D (2009) S-Nitrosothiols in blood: does photosensitivity explain a 4-order-of-magnitude concentration range? Clin Chem 55:1036–1038

    Article  CAS  PubMed  Google Scholar 

  46. Schapiro S, Salas M, Vukovich K (1970) Hormonal effects on ontogeny of swimming ability in the rat: assessment of central nervous system development. Science 168:147–151

    Article  CAS  PubMed  Google Scholar 

  47. Schneider T, Przewłocki R (2005) Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism. Neuropsychopharmacology 30:80–89

    Article  CAS  PubMed  Google Scholar 

  48. Sharma N, Ahmad Y (2011) An effective method for the analysis of human plasma proteome using two-dimensional gel electrophoresis. Journal of Proteomics & Bioinformatics 2009

  49. Simopoulos AP (1991) Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr 54:438–463

    CAS  PubMed  Google Scholar 

  50. Sliwinski S, Croonenberghs J, Christophe A, Deboutte D, Maes M (2006) Polyunsaturated fatty acids: do they have a role in the pathophysiology of autism? Neuro endocrinology letters 27:465–471

    CAS  PubMed  Google Scholar 

  51. Souza A, Dussan-Sarria JA, Medeiros LF, Souza AC, Oliveira C, Scarabelot VL, Adachi LN, Winkelmann-Duarte EC, Philippi-Martins BB, Netto CA (2014) Neonatal hypoxic–ischemic encephalopathy reduces c-Fos activation in the rat hippocampus: evidence of a long-lasting effect. Int J Dev Neurosci 38:213–222

    Article  CAS  PubMed  Google Scholar 

  52. Spencer L, Mann C, Metcalfe M, Webb MB, Pollard C, Spencer D, Berry D, Steward W, Dennison A (2009) The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Eur J Cancer 45:2077–2086

    Article  CAS  PubMed  Google Scholar 

  53. Teitelbaum JE, Walker WA (2001) Review: the role of omega 3 fatty acids in intestinal inflammation. J Nutr Biochem 12:21–32

    Article  CAS  PubMed  Google Scholar 

  54. Theoharides TC, Asadi S, Patel AB (2013) Focal brain inflammation and autism. J Neuroinflammation 10:1

    Article  Google Scholar 

  55. Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci 76:4350–4354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Weidenheim KM (2001) Neurobiology of autism: an update. Salud Mental 24:3–9

    Google Scholar 

  57. Wenning GK, Jellinger KA (2005) The role of α-synuclein in the pathogenesis of multiple system atrophy. Acta Neuropathol 109:129–140

    Article  CAS  PubMed  Google Scholar 

  58. Zoroglu SS, Armutcu F, Ozen S, Gurel A, Sivasli E, Yetkin O, Meram I (2004) Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. Eur Arch Psychiatry Clin Neurosci 254:143–147

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the University Grants Commission for providing fellowship to MS, JKR, SG, and RKY and would also like to thank to the Department of Science and Technology for providing fellowship to SR.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), VidyaVihar, Raebareli Road, Lucknow, UP, 226 025, India

    Sneha Yadav, Virendra Tiwari, Manjari Singh, Rajnish K. Yadav, Subhadeep Roy, Swetlana Gautam, Jitendra Kumar Rawat, Shubhini A. Saraf & Gaurav Kaithwas

  2. Department of Pharmaceutical Sciences, Faculty of Health Medical Sciences Indigenous and Alternative Medicine, SHIATS- Deemed to be University, Formerly Allahabad Agricultural Institute, Naini, Allahabad, UP, India

    Uma Devi

  3. Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AL-Kharj, Kingdom of Saudi Arabia

    Mohd. Nazam Ansari & Abdulaziz Sa Saeedan

  4. Department of Biotechnology, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), VidyaVihar Raebareli Road, Lucknow, UP, 226 025, India

    Anand Prakash

Authors
  1. Sneha Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Virendra Tiwari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manjari Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rajnish K. Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Subhadeep Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Uma Devi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Swetlana Gautam
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jitendra Kumar Rawat
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mohd. Nazam Ansari
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Abdulaziz Sa Saeedan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Anand Prakash
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shubhini A. Saraf
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Gaurav Kaithwas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gaurav Kaithwas.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Sneha Yadav and Virendra Tiwari have equal contribution.

Electronic supplementary material

Supplementary Figure 1

FAME of the brain tissue subjected to ALA and GLA. Group I: control (3 ml/kg), group II: positive control (400 mg/kg), group III: ALA(3 ml/kg), group IV: GLA(3 ml/kg), group V: VPA + ALA(400 mg/kg + 3 ml/kg), and group VI:VPA + GLA(400 mg/kg + 3 ml/kg) (DOCX 106 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yadav, S., Tiwari, V., Singh, M. et al. Comparative efficacy of alpha-linolenic acid and gamma-linolenic acid to attenuate valproic acid-induced autism-like features. J Physiol Biochem 73, 187–198 (2017). https://doi.org/10.1007/s13105-016-0532-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-016-0532-2

Keywords

Search

Navigation