Journal of Physiology and Biochemistry

, Volume 73, Issue 2, pp 187–198 | Cite as

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

  • Sneha Yadav
  • Virendra Tiwari
  • Manjari Singh
  • Rajnish K. Yadav
  • Subhadeep Roy
  • Uma Devi
  • Swetlana Gautam
  • Jitendra Kumar Rawat
  • Mohd. Nazam Ansari
  • Abdulaziz Sa Saeedan
  • Anand Prakash
  • Shubhini A. Saraf
  • Gaurav Kaithwas
Original Article

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.

Keywords

Alpha-linolenic acid Autism spectrum disorder Gamma-linolenic acid Pgp 9.5 Polyunsaturated fatty acids 

Supplementary material

13105_2016_532_MOESM1_ESM.docx (107 kb)
Supplementary Figure 1FAME 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)

References

  1. 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 42:1032–1040CrossRefPubMedGoogle Scholar
  2. 2.
    Altman J, Sudarshan K (1975) Postnatal development of locomotion in the laboratory rat. Anim Behav 23:896–920CrossRefPubMedGoogle Scholar
  3. 3.
    Anand R, Kaithwas G (2014) Anti-inflammatory potential of alpha-linolenic acid mediated through selective COX inhibition: computational and experimental data. Inflammation 37:1297–1306CrossRefPubMedGoogle Scholar
  4. 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 1408:8–16CrossRefPubMedGoogle Scholar
  5. 5.
    Bauman M, Kemper TL (1985) Histoanatomic observations of the brain in early infantile autism. Neurology 35:866–866CrossRefPubMedGoogle Scholar
  6. 6.
    Bauman ML, Kemper TL (2005) Neuroanatomic observations of the brain in autism: a review and future directions. Int J Dev Neurosci 23:183–187CrossRefPubMedGoogle Scholar
  7. 7.
    Belch JJ, Hill A (2000) Evening primrose oil and borage oil in rheumatologic conditions. Am J Clin Nutr 71:352s–356sPubMedGoogle Scholar
  8. 8.
    Belur B, Kandaswamy N, Mukherjee K (1990) Laboratory techniques in histopathology. Medical laboratory technologyGoogle Scholar
  9. 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 41:545–554CrossRefPubMedGoogle Scholar
  10. 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 1:104CrossRefPubMedPubMedCentralGoogle Scholar
  11. 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 110:3489–3494CrossRefPubMedPubMedCentralGoogle Scholar
  12. 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 103–117Google Scholar
  13. 13.
    Covington MB (2004) Omega-3 fatty acids. Atlantic 1:2.0Google Scholar
  14. 14.
    Crane FL, Low H, Sun IL (2012) Evidence for a relation between plasma membrane coenzyme Q and autism. Frontiers in bioscience (Elite edition) 5:1011–1016Google Scholar
  15. 15.
    Croen LA, Grether JK, Hoogstrate J, Selvin S (2002) The changing prevalence of autism in California. J Autism Dev Disord 32:207–215CrossRefPubMedGoogle Scholar
  16. 16.
    Cullen L, Kelly L, Connor SO, Fitzgerald DJ (1998) Selective cyclooxygenase-2 inhibition by nimesulide in man. J Pharmacol Exp Ther 287:578–582PubMedGoogle Scholar
  17. 17.
    Daynes RA, Jones DC (2002) Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol 2:748–759CrossRefPubMedGoogle Scholar
  18. 18.
    Depino AM (2013) Peripheral and central inflammation in autism spectrum disorders. Mol Cell Neurosci 53:69–76CrossRefPubMedGoogle Scholar
  19. 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 10:1CrossRefGoogle Scholar
  20. 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 5:160–179CrossRefPubMedPubMedCentralGoogle Scholar
  21. 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 226:497–509PubMedGoogle Scholar
  22. 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 126:775–788CrossRefPubMedGoogle Scholar
  23. 23.
    Haas H, Schauenstein K (2001) Immunity, hormones, and the brain. Allergy 56:470–477CrossRefPubMedGoogle Scholar
  24. 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 114:1237–1245CrossRefGoogle Scholar
  25. 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 3:428–437Google Scholar
  26. 26.
    Kaithwas G, Mukerjee A, Kumar P, Majumdar DK (2011a) Linum usitatissimum (linseed/flaxseed) fixed oil: antimicrobial activity and efficacy in bovine mastitis. Inflammopharmacology 19:45–52CrossRefPubMedGoogle Scholar
  27. 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):932–938PubMedGoogle Scholar
  28. 28.
    Kapoor R, Huang Y-S (2006) Gamma linolenic acid: an antiinflammatory omega-6 fatty acid. Curr Pharm Biotechnol 7:531–534CrossRefPubMedGoogle Scholar
  29. 29.
    Karvat G, Kimchi T (2014) Acetylcholine elevation relieves cognitive rigidity and social deficiency in a mouse model of autism. Neuropsychopharmacology 39:831–840CrossRefPubMedGoogle Scholar
  30. 30.
    Kern JK, Geier DA, Sykes LK, Geier MR (2013) Evidence of neurodegeneration in autism spectrum disorder. Translational neurodegeneration 2:1CrossRefGoogle Scholar
  31. 31.
    Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685CrossRefPubMedGoogle Scholar
  32. 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 441:162–168CrossRefPubMedGoogle Scholar
  33. 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 :kws433Google Scholar
  34. 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 82:477–488CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Meiri G, Bichovsky Y, Belmaker R (2009) Omega 3 fatty acid treatment in autism. Journal of child and adolescent psychopharmacology 19:449–451CrossRefPubMedGoogle Scholar
  36. 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 9Google Scholar
  37. 37.
    Nader R, Oberlander TF, Chambers CT, Craig KD (2004) Expression of pain in children with autism. Clin J Pain 20:88–97CrossRefPubMedGoogle Scholar
  38. 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 6:222–227CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Poling JS, Frye RE, Shoffner J, Zimmerman AW (2006) Developmental regression and mitochondrial dysfunction in a child with autism. J Child Neurol 21:170–172CrossRefPubMedPubMedCentralGoogle Scholar
  40. 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 4:60397–60403CrossRefGoogle Scholar
  41. 41.
    Reznick AZ, Packer L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 233:357–363CrossRefPubMedGoogle Scholar
  42. 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 296:558–566PubMedGoogle Scholar
  43. 43.
    Rolf L, Haarmann F, Grotemeyer KH, Kehrer H (1993) Serotonin and amino acid content in platelets of autistic children. Acta Psychiatr Scand 87:312–316CrossRefPubMedGoogle Scholar
  44. 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:e85436CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Rossi R, Tsikas D (2009) S-Nitrosothiols in blood: does photosensitivity explain a 4-order-of-magnitude concentration range? Clin Chem 55:1036–1038CrossRefPubMedGoogle Scholar
  46. 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 168:147–151CrossRefPubMedGoogle Scholar
  47. 47.
    Schneider T, Przewłocki R (2005) Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism. Neuropsychopharmacology 30:80–89CrossRefPubMedGoogle Scholar
  48. 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 2009Google Scholar
  49. 49.
    Simopoulos AP (1991) Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr 54:438–463PubMedGoogle Scholar
  50. 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 27:465–471PubMedGoogle Scholar
  51. 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 38:213–222CrossRefPubMedGoogle Scholar
  52. 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 45:2077–2086CrossRefPubMedGoogle Scholar
  53. 53.
    Teitelbaum JE, Walker WA (2001) Review: the role of omega 3 fatty acids in intestinal inflammation. J Nutr Biochem 12:21–32CrossRefPubMedGoogle Scholar
  54. 54.
    Theoharides TC, Asadi S, Patel AB (2013) Focal brain inflammation and autism. J Neuroinflammation 10:1CrossRefGoogle Scholar
  55. 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 76:4350–4354CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Weidenheim KM (2001) Neurobiology of autism: an update. Salud Mental 24:3–9Google Scholar
  57. 57.
    Wenning GK, Jellinger KA (2005) The role of α-synuclein in the pathogenesis of multiple system atrophy. Acta Neuropathol 109:129–140CrossRefPubMedGoogle Scholar
  58. 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 254:143–147CrossRefPubMedGoogle Scholar

Copyright information

© University of Navarra 2016

Authors and Affiliations

  • Sneha Yadav
    • 1
  • Virendra Tiwari
    • 1
  • Manjari Singh
    • 1
  • Rajnish K. Yadav
    • 1
  • Subhadeep Roy
    • 1
  • Uma Devi
    • 2
  • Swetlana Gautam
    • 1
  • Jitendra Kumar Rawat
    • 1
  • Mohd. Nazam Ansari
    • 3
  • Abdulaziz Sa Saeedan
    • 3
  • Anand Prakash
    • 4
  • Shubhini A. Saraf
    • 1
  • Gaurav Kaithwas
    • 1
  1. 1.Department of Pharmaceutical Sciences, School of Biosciences and BiotechnologyBabasaheb Bhimrao Ambedkar University (A Central University)LucknowIndia
  2. 2.Department of Pharmaceutical Sciences, Faculty of Health Medical Sciences Indigenous and Alternative MedicineSHIATS- Deemed to be University, Formerly Allahabad Agricultural InstituteNaini, AllahabadIndia
  3. 3.Department of Pharmacology, College of PharmacyPrince Sattam Bin Abdulaziz UniversityAL-KharjKingdom of Saudi Arabia
  4. 4.Department of Biotechnology, School of Biosciences and BiotechnologyBabasaheb Bhimrao Ambedkar University (A Central University)LucknowIndia

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