Deneysel Otizm Spektrum Bozukluğu Modeli Oluşturulan Sıçanlarda Likopenin Beyin IL–6, IL–10, FGF–2 ve NGF Düzeyleri Üzerine Etkisi

Year 2020, , 139 - 143, 31.12.2020

Füsun Erten , Hasan Gençoğlu , Kazim Şahin

https://doi.org/10.47027/duvetfd.825114

Abstract

Otizm spektrum bozukluğu (OSB), batılı ve gelişmiş toplumlarda artan bir sorundur. Doğası gereği büyük ölçüde genetik olmasına rağmen, birçok çevresel faktör hassas popülasyonlarda OSB'yi tetiklemede rol oynayabilmektedir. Propiyonik asit (PPA) uygulaması, anormal nöral hücre organizasyonunu ve ardından otizm benzeri nörodavranışları içeren kritik değişiklikleri indükleyebilmektedir. Likopen ve metabolitleri beyinde kontrol edilebildiğinden, likopenin merkezi sinir sisteminde nöroprotektif etkileri olabileceği ve başlıca beyin biyo-belirteçleri üzerinde modülasyona neden olabileceği düşünülmektedir. Bu çalışmada, 35 adet üç haftalık yaşta Sprague Dawley ırkı erkek sıçan 5 gruba ayrıldı: i) Kontrol. ii) PPA; (500 mg/kg/ip). iii) PPA+LI (PPA’ya ek olarak, 5 mg/kg/gün intragastrik likopen verilen grup), iv) PPA+LII; (PPA’ya ek olarak, 10 mg/kg/gün intragastrik likopen verilen grup), v) PPA+LIII, (PPA’ya ek olarak, 20 mg/kg/gün intragastrik likopen verilen grup). Çalışma sonunda hayvanlar dekapite edildi ve beyin dokuları alınarak homojenize edildi ve SDS-PAGE ve western blot teknikleriyle beyinde enflamatuar sitokinler interlökin 6 ve 10’un (IL6/IL10) ile temel fibroblast büyüme faktörü (FGF-2) ve sinir büyüme faktörü (NGF) düzeylerinin değişimi tespit edildi. Elde edilen sonuçlara göre 35 günlük uygulama sonunda likopenin, PPA ile OSB modeli oluşturulan sıçanlarda, PPA’ya bağlı olarak artan IL–6 ve IL-10 düzeylerini özellikle PPA+LIII ve PPA+LII grubunda düşürdüğü tespit edildi. Bununla birlikte, FGF–2 ve NGF düzeyleri de her üç likopen grubunda da belirgin olarak PPA verilen gruba göre artış gösterdi (P<0,0001). Sonuç olarak, likopen, PPA ile indüklenen OSB benzeri nöropatolojik bozuklukları beyin inflamatuar sitokinleri ve büyüme faktörlerini regüle ederek azaltabilir.

Keywords

likopen, otizm, propiyonik asit, sıçan modeli

References

• Mirza R, Sharma B. (2018). Selective modulator of peroxisome proliferator-activated receptor-α protects propionic acid induced autism-like phenotypes in rats. Life Sci. 214: 106–117.
• Bhandari R, Kuhad A. (2015). Neuropsychopharmacotherapeutic efficacy of curcumin in experimental paradigm of autism spectrum disorders. Life Sci. 141: 156–169.
• Shultz SR, Aziz NAB, Yang L, Sun M, MacFabec DF, O’Briena TJ. (2015). Intracerebroventricular injection of propionic acid, an enteric metabolite implicated in autism. induces social abnormalities that do not differ between seizure prone (FAST) and seizure-resistant (SLOW) rats. Behav Brain Res. 278: 542–548.
• El-Ansary A, Al-Ghamdi M, Bhat RS, Al-daihanSooad AL. (2016). Potency of pre–post treatment of coenzyme Q10 and melatonin supplement in ameliorating the impaired fatty acid profile in rodent model of autism. Food Nutr. Res. 60: 10.
• Xu FL, Fan T, Duan JJ, Chen D. (2012). Clinical analysis of organic acidemia in neonates from neonatal intensive care units. Zhongguo Dang Dai Er Ke Za Zhi. 14: 336–339.
• Khalil SR, Abd-Elhakim YM, Selim ME, Al-Ayadhi LY. (2015). Apitoxin protects rat pups brain from propionic acid-induced oxidative stress: The expression pattern of Bcl-2 and Caspase-3 apoptotic genes. NeuroToxicology. 49: 121–131.
• Gupta R, Deshpande SB. (2008). 3-Nitropropionic acid depresses spinal reflexes involving GABA ergic and glycinergic transmission in neonatal rat spinal cord in vitro. Life Sci. 83: 756–760.
• Shultz SR, MacFabe DF, Ossenkopp KP, Scratch S, Whelan J, Taylor R, Cain DP. (2008). Intracerebroventricular injection of propionic acid, an enteric bacterial metabolic end product, impairs social behavior in the rat: implications for an animal model of autism. Neuropharmacology. 54: 901–911.
• Thomas RH, Foley KA, Mepham JR, Tichenoff LJ, Possmayer F, MacFabe DF. (2010). Altered brain phospholipid and acylcarnitine profiles in propionic acid infused rodents; further development of a potential model of autism spectrum disorders. J. Neurochem. 113: 515–529.
• Heber D, Lu QY. (2002). Overview of mechanisms of action of lycopene. Exp. Biol. Med. (Maywood). 227: 920–923.
• Sahin K, Gencoglu H, Bilir B, Kucuk O. (2018). The Liver. (İçinde): Chapter 14 - Protective Role of Lycopene against Oxidative Stress in Liver. Patel VB, Rajendram R, Preedy VR (editörler). Cilt 1. Baskı 1. s. 155–67. Academic Press. Boston, ABD. https://doi.org/10.1016/B978-0-12-803951-9.00014-8.
• Yu L, Wang W, Pang W, Xiao Z, Jiang Y, Hong Y. (2017). Diatery lycopene supplematation improves cognitive performances in Tau transgenic mice expressing P301L mutation via inhibiting oxidative stress and Tau hyperphosphorylation. J.Alzheimers Dis. 57: 475–482.
• Chen D, Huang C, Chen Z. (2019). Review: A review for the pharmacological effect of lycopene in central nervous system disorders. Biomedicine & Pharmacotherapy. 111: 791–801.
• Lei X, Lei L, Zhang Z, Cheng Y. (2016). Neuroprotective effects of lycopene pretreatment on transient global cerebral ischemia-reperfusion in rats: the role of the Nrf2/HO-1 signaling pathway. Mol. Med. Rep. 13: 412–418.
• Hu W, Wang H, Liu Z, Liu Y, Wang R, Luo X, Huang Y. (2017). Neuroprotective effects of lycopene in spinal cord injury in rats via antioxidative and anti-apoptotic pathway. Neurosci Lett. 642: 107–112. https://doi.org/10.1016/j.neulet.2017.02.004.
• Liu CB, Wang R, Yi YF, Gao Z, Chen YZ. (2018). Lycopene mitigates β-amyloid induced inflammatory response and inhibits NF-κB signaling at the choroid plexus in early stages of Alzheimer’s disease rats. J Nutr Biochem. 53: 66–71. https://doi.org/10.1016/j.jnutbio.2017.10.014.
• Choi J, Lee S, Won J, Jin Y, Hong Y, Hur TY, Kim JH, Lee SR, Hong Y. (2018). Pathophysiological and neurobehavioral characteristics of a propionic acid-mediated autism-like rat model. PLoS One. 13: e0192925. https://doi.org/10.1371/journal.pone.0192925.
• El Morsy EM, Ahmed M. (2020). Protective effects of lycopene on hippocampal neurotoxicity and memory impairment induced by bisphenol A in rats. Hum Exp Toxicol. 39(8): 1066-1078. https://doi.org/10.1177/0960327120909882.
• Prakash A, Kumar A. (2013). Lycopene protects against memory impairment and mito-oxidative damage induced by colchicine in rats: an evidence of nitric oxide signaling. Eur J Pharmacol. 721: 373-381. https://doi.org/10.1016/j.ejphar.2013.08.016.
• Saghazadeh A, Ataeinia B, Keynejad K, Abdolalizadeh A, Hirbod-Mobarakeh A, Rezaei N. (2019). A meta-analysis of pro-inflammatory cytokines in autism spectrum disorders; effects of age, gender, and latitude. J Psychiatr Res. 115: 90–102. https://doi.org/10.1016/j.jpsychires.2019.05.019.
• Li F, Xiang H, Lu J, Chen Z, Huang C, Yuan X. (2020). Lycopene ameliorates PTSD-like behaviors in mice and rebalances the neuroinflammatory response and oxidative stress in the brain. Physiol Behav. 224: 113026. https://doi.org/10.1016/j.physbeh.2020.113026.
• Ornitz, DM, Itoh N. (2015). The Fibroblast Growth Factor signaling pathway. Wiley Interdisciplinary Reviews. Developmental Biology. 4(3): 215–266.
• Reuss B, von Bohlen und Halbach O. (2003). Fibroblast growth factors and their receptors in the central nervous system. Cell Tissue Res. 313: 139-157.
• Pase CS, Teixeira AM, Roversi K, Dias VT, Calabrese F, Molteni R, Franchi S, Panerai AE, Riva MA, Burger ME. (2015). Olive oil-enriched diet reduces brain oxidative damages and ameliorates neurotrophic factor gene expression in different life stages of rats. The Journal of Nutritional Biochemistry. 26(11): 1200–1207.
• Aloe L, Rocco ML, Bianchi P, Manni L. (2012). Nerve growth factor: from the early discoveries to the potential clinical use. J Transl Med. 10:239.
• Yang W, Shen Z, Wen S, Wang W, Hu M. (2018). Mechanisms of multiple neurotransmitters in the effects of Lycopene on brain injury induced by Hyperlipidemia. Lipids Health Dis. 17: 13.
• Holtzman DM, Sheldon RA, Jaffe W, Cheng Y, Ferriero DM. (1996). Nerve growth factor protects the neonatal brain against hypoxic-ischemic injury. Ann Neurol. 39(1): 114–122.
• Nai Y, Liu H, Bi X, Gao H, Ren C. (2018). Protective effect of astaxanthin on acute cerebral infarction in rats. Hum Exp Toxicol. 37(9): 929–936.