Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
September-2016 Volume 12 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2016 Volume 12 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Increased expression of fatty acid synthase and acetyl‑CoA carboxylase in the prefrontal cortex and cerebellum in the valproic acid model of autism

  • Authors:
    • Jianling Chen
    • Wei Wu
    • Yingmei Fu
    • Shunying Yu
    • Donghong Cui
    • Min Zhao
    • Yasong Du
    • Jijun Li
    • Xiaohong Li
  • View Affiliations / Copyright

    Affiliations: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China, Department of Pathology, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, P.R. China, Department of Integrative Medicine on Pediatrics, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1293-1298
    |
    Published online on: July 5, 2016
       https://doi.org/10.3892/etm.2016.3508
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The primary aim of the present study was to investigate alterations in enzymes associated with fatty acid synthesis, namely fatty acid synthase (FASN) and acetyl‑CoA carboxylase (ACC), in the prefrontal cortex and cerebellum of the valproic acid (VPA)‑induced animal model of autism. In this model, pregnant rats were given a single intraperitoneal injection of VPA, and prefrontal cortex and cerebellum samples from their pups were analyzed. The results of western blotting and reverse transcription‑quantitative polymerase chain reaction analyses demonstrated that the protein and mRNA expression levels of FASN, ACC and phospho‑ACC (pACC) were increased in the prefrontal cortex and cerebellum of the VPA model of autism. Furthermore, in the prefrontal cortex and cerebellum of the VPA model of autism, AMPK expression is increased, whereas PI3K and Akt expression are unchanged. This suggests that disorder of the phosphatidylinositol‑4,5-bisphosphate 3‑kinase (PI3K)/Akt/FASN and/or adenosine 5'‑monophosphate‑activated protein kinase (AMPK)/ACC pathway may be involved in the pathogenesis of autism. It is hypothesized that fatty acid synthesis participates in autism through PI3K/Akt/FASN and AMPK/ACC pathways.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (5th). American Psychiatric Publishing. Arlington, VA: 2013.

2 

Ornoy A: Valproic acid in pregnancy: How much are we endangering the embryo and fetus? Reprod Toxicol. 28:1–10. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Rodier PM, Ingram JL, Tisdale B and Croog VJ: Linking etiologies in humans and animal models: Studies of autism. Reprod Toxicol. 11:417–422. 1997. View Article : Google Scholar : PubMed/NCBI

4 

Chomiak T and Hu B: Alterations of neocortical development and maturation in autism: Insight from valproic acid exposure and animal models of autism. Neurotoxicol Teratol. 36:57–66. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Foley AG, Gannon S, Rombach-Mullan N, Prendergast A, Barry C, Cassidy AW and Regan CM: Class I histone deacetylase inhibition ameliorates social cognition and cell adhesion molecule plasticity deficits in a rodent model of autism spectrum disorder. Neuropharmacology. 63:750–760. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Bauman ML: Microscopic neuroanatomic abnormalities in autism. Pediatrics. 87:791–796. 1991.PubMed/NCBI

7 

Zhao G, Gao J, Liang S, Wang X, Sun C, Xia W, Hao Y, Li X, Cao Y and Wu L: Study of the serum levels of polyunsaturated fatty acids and the expression of related liver metabolic enzymes in a rat valproate-induced autism model. Int J Dev Neurosci. 44:14–21. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Brigandi SA, Shao H, Qian SY, Shen Y, Wu BL and Kang JX: Autistic children exhibit decreased levels of essential fatty acids in red blood cells. Int J Mol Sci. 16:10061–10076. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Saito M, Chakraborty G, Mao RF and Vadasz C: Developmental profiles of lipogenic enzymes and their regulators in the neonatal mouse brain. Neurochem Res. 34:1945–1954. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Spencer EB, Bianchi A, Widmer J and Witters LA: Brain acetyl-CoA carboxylase: Isozymic identification and studies of its regulation during development and altered nutrition. Biochem Biophys Res Commun. 192:820–825. 1993. View Article : Google Scholar : PubMed/NCBI

11 

Schneider T and Przewłocki R: Behavioral alterations in rats prenatally exposed to valproic acid: Animal model of autism. Neuropsychopharmacology. 30:80–89. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Ha J, Daniel S, Broyles SS and Kim KH: Critical phosphorylation sites for acetyl-CoA carboxylase activity. J Biol Chem. 269:22162–22168. 1994.PubMed/NCBI

14 

Schultz ST, Klonoff-Cohen HS, Wingard DL, Akshoomoff NA, Macera CA, Ji M and Bacher C: Breastfeeding, infant formula supplementation and autistic disorder: The results of a parent survey. Int Breastfeed J. 1:162006. View Article : Google Scholar : PubMed/NCBI

15 

Meguid NA, Atta HM, Gouda AS and Khalil RO: Role of polyunsaturated fatty acids in the management of Egyptian children with autism. Clin Biochem. 41:1044–1048. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Lea W, Abbas AS, Sprecher H, Vockley J and Schulz H: Long-chain acyl-CoA dehydrogenase is a key enzyme in the mitochondrial beta-oxidation of unsaturated fatty acids. Biochim Biophys Acta. 1485:121–128. 2000. View Article : Google Scholar : PubMed/NCBI

17 

Cox KB, Hamm DA, Millington DS, Matern D, Vockley J, Rinaldo P, Pinkert CA, Rhead WJ, Lindsey JR and Wood PA: Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse. Hum Mol Genet. 10:2069–2077. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Clark-Taylor T and Clark-Taylor BE: Is autism a disorder of fatty acid metabolism? Possible dysfunction of mitochondrial beta-oxidation by long chain acyl-CoA dehydrogenase. Med Hypotheses. 62:970–975. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jörnvall H, Kavanagh KL, Kedishvili N, et al: The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative. Chem Biol Interact. 178:94–98. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Veigel D, Wagner R, Stübiger G, Wuczkowski M, Filipits M, Horvat R, Benhamú B, López-Rodríguez ML, Leisser A, Valent P, et al: Fatty acid synthase is a metabolic marker of cell proliferation rather than malignancy in ovarian cancer and its precursor cells. Int J Cancer. 136:2078–2090. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Pucilowska J, Vithayathil J, Tavares EJ, Kelly C, Karlo JC and Landreth GE: The 16p11.2 deletion mouse model of autism exhibits altered cortical progenitor proliferation and brain cytoarchitecture linked to the ERK MAPK pathway. J Neurosci. 35:3190–3200. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Yang K, Cao F, Sheikh AM, Malik M, Wen G, Wei H, Brown WT and Li X: Up-regulation of Ras/Raf/ERK1/2 signaling impairs cultured neuronal cell migration, neurogenesis, synapse formation, and dendritic spine development. Brain Struct Funct. 218:669–682. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Cao FJ, Zhang X, Liu T, Li XW, Malik M and Feng SQ: Up-regulation of Ras/Raf/ERK1/2 signaling in the spinal cord impairs neural cell migration, neurogenesis, synapse formation, and dendritic spine development. Chin Med J (Engl). 126:3879–3885. 2013.PubMed/NCBI

24 

Grunt TW, Wagner R, Grusch M, Berger W, Singer CF, Marian B, Zielinski CC and Lupu R: Interaction between fatty acid synthase- and ErbB-systems in ovarian cancer cells. Biochem Biophys Res Commun. 385:454–459. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Long XH, Zhang GM, Peng AF, Luo QF, Zhang L, Wen HC, Zhou RP, Gao S, Zhou Y and Liu ZL: Lapatinib alters the malignant phenotype of osteosarcoma cells via downregulation of the activity of the HER2-PI3K/AKT-FASN axis in vitro. Oncol Rep. 31:328–334. 2014.PubMed/NCBI

26 

Chen J, Alberts I and Li X: Dysregulation of the IGF-I/PI3K/AKT/mTOR signaling pathway in autism spectrum disorders. Int J Dev Neurosci. 35:35–41. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Abu-Elheiga L, Matzuk MM, Abo-Hashema KA and Wakil SJ: Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science. 291:2613–2616. 2001. View Article : Google Scholar : PubMed/NCBI

28 

Nelson DL and Cox MM: Lehninger Principles of Biochemistry (5th). W. H. Freeman and Company. London: 8062008.

29 

Giulivi C, Zhang YF, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, Tassone F and Pessah IN: Mitochondrial dysfunction in autism. JAMA. 304:2389–2396. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Frye RE, Melnyk S and Macfabe DF: Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder. Transl Psychiatry. 3:e2202013. View Article : Google Scholar : PubMed/NCBI

31 

Thomas RH, Foley KA, Mepham JR, Tichenoff LJ, Possmayer F and MacFabe DF: 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. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Avery LB and Bumpus NN: Valproic acid is a novel activator of AMP-activated protein kinase and decreases liver mass, hepatic fat accumulation and serum glucose in obese mice. Mol Pharmacol. 85:1–10. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Wen JP, Liu CE, Hu YT, Chen G and Lin LX: Globular adiponectin regulates energy homeostasis through AMP-activated protein kinase-acetyl-CoA carboxylase (AMPK/ACC) pathway in the hypothalamus. Mol Cell Biochem. 344:109–115. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Ahn Y, Narous M, Tobias R, Rho JM and Mychasiuk R: The ketogenic diet modifies social and metabolic alterations identified in the prenatal valproic acid model of autism spectrum disorder. Dev Neurosci. 36:371–380. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Jeon BT, Lee DH, Kim KH, Kim HJ, Kang SS, Cho GJ, Choi WS and Roh GS: Ketogenic diet attenuates kainic acid-induced hippocampal cell death by decreasing AMPK/ACC pathway activity and HSP70. Neurosci Lett. 453:49–53. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen J, Wu W, Fu Y, Yu S, Cui D, Zhao M, Du Y, Li J and Li X: Increased expression of fatty acid synthase and acetyl‑CoA carboxylase in the prefrontal cortex and cerebellum in the valproic acid model of autism. Exp Ther Med 12: 1293-1298, 2016.
APA
Chen, J., Wu, W., Fu, Y., Yu, S., Cui, D., Zhao, M. ... Li, X. (2016). Increased expression of fatty acid synthase and acetyl‑CoA carboxylase in the prefrontal cortex and cerebellum in the valproic acid model of autism. Experimental and Therapeutic Medicine, 12, 1293-1298. https://doi.org/10.3892/etm.2016.3508
MLA
Chen, J., Wu, W., Fu, Y., Yu, S., Cui, D., Zhao, M., Du, Y., Li, J., Li, X."Increased expression of fatty acid synthase and acetyl‑CoA carboxylase in the prefrontal cortex and cerebellum in the valproic acid model of autism". Experimental and Therapeutic Medicine 12.3 (2016): 1293-1298.
Chicago
Chen, J., Wu, W., Fu, Y., Yu, S., Cui, D., Zhao, M., Du, Y., Li, J., Li, X."Increased expression of fatty acid synthase and acetyl‑CoA carboxylase in the prefrontal cortex and cerebellum in the valproic acid model of autism". Experimental and Therapeutic Medicine 12, no. 3 (2016): 1293-1298. https://doi.org/10.3892/etm.2016.3508
Copy and paste a formatted citation
x
Spandidos Publications style
Chen J, Wu W, Fu Y, Yu S, Cui D, Zhao M, Du Y, Li J and Li X: Increased expression of fatty acid synthase and acetyl‑CoA carboxylase in the prefrontal cortex and cerebellum in the valproic acid model of autism. Exp Ther Med 12: 1293-1298, 2016.
APA
Chen, J., Wu, W., Fu, Y., Yu, S., Cui, D., Zhao, M. ... Li, X. (2016). Increased expression of fatty acid synthase and acetyl‑CoA carboxylase in the prefrontal cortex and cerebellum in the valproic acid model of autism. Experimental and Therapeutic Medicine, 12, 1293-1298. https://doi.org/10.3892/etm.2016.3508
MLA
Chen, J., Wu, W., Fu, Y., Yu, S., Cui, D., Zhao, M., Du, Y., Li, J., Li, X."Increased expression of fatty acid synthase and acetyl‑CoA carboxylase in the prefrontal cortex and cerebellum in the valproic acid model of autism". Experimental and Therapeutic Medicine 12.3 (2016): 1293-1298.
Chicago
Chen, J., Wu, W., Fu, Y., Yu, S., Cui, D., Zhao, M., Du, Y., Li, J., Li, X."Increased expression of fatty acid synthase and acetyl‑CoA carboxylase in the prefrontal cortex and cerebellum in the valproic acid model of autism". Experimental and Therapeutic Medicine 12, no. 3 (2016): 1293-1298. https://doi.org/10.3892/etm.2016.3508
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team