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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
February-2015 Volume 11 Issue 2

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
February-2015 Volume 11 Issue 2

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

Increased immunoreactivity of c‑Fos in the spinal cord of the aged mouse and dog

  • Authors:
    • Ji Hyeon Ahn
    • Myoung Chul Shin
    • Joon Ha Park
    • In Hye Kim
    • Jae‑Chul Lee
    • Bing Chun Yan
    • In Koo Hwang
    • Seung Myung Moon
    • Ji Yun Ahn
    • Taek Geun Ohk
    • Tae Hun Lee
    • Jun Hwi Cho
    • Hyung‑Cheul Shin
    • Moo‑Ho Won
  • View Affiliations / Copyright

    Affiliations: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea, Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea, Institute of Integrative Traditional and Western Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul 151‑742, Republic of Korea, Department of Neurosurgery, Dongtan Sacred Heart Hospital, College of Medicine, Hallym University, Hwaseong, Gyeonggi 445‑170, Republic of Korea, Department of Emergency Medicine, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chuncheon, Gangwon 200‑702, Republic of Korea, Department of Physiology, College of Medicine, Hallym University, Chuncheon, Gangwon 200‑702, Republic of Korea
  • Pages: 1043-1048
    |
    Published online on: October 29, 2014
       https://doi.org/10.3892/mmr.2014.2800
  • 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

Expression of c‑Fos in the spinal cord following nociceptive stimulation is considered to be a neurotoxic biomarker. In the present study, the immunoreactivity of c‑Fos in the spinal cord was compared between young adult (2‑3 years in dogs and 6 months in mice) and aged (10‑12 years in dogs and 24 months in mice) Beagle dogs and C57BL/6J mice. In addition, changes to neuronal distribution and damage to the spinal cord were also investigated. There were no significant differences in neuronal loss or degeneration of the spinal neurons observed in either the aged dogs or mice. Weak c‑Fos immunoreactivity was observed in the spinal neurons of the young adult animals; however, c‑Fos immunoreactivity was markedly increased in the nuclei of spinal neurons in the aged dogs and mice, as compared with that of the young adults. In conclusion, c‑Fos immunoreactivity was significantly increased without any accompanying neuronal loss in the aged spinal cord of mice and dogs, as compared with the spinal cords of the young adult animals.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Gibson SJ and Helme RD: Age-related differences in pain perception and report. Clin Geriatr Med. 17:433–456. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Helme RD and Gibson SJ: The epidemiology of pain in elderly people. Clin Geriatr Med. 17:417–431. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Werhagen L, Budh CN, Hultling C and Molander C: Neuropathic pain after traumatic spinal cord injury - relations to gender, spinal level, completeness, and age at the time of injury. Spinal Cord. 42:665–673. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Schmader KE: Epidemiology and impact on quality of life of postherpetic neuralgia and painful diabetic neuropathy. Clin J Pain. 18:350–354. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Coggeshall RE: Fos, nociception and the dorsal horn. Prog Neurobiol. 77:299–352. 2005.PubMed/NCBI

6 

Munglani R, Hudspith MJ, Fleming B, et al: Effect of pre-emptive NMDA antagonist treatment on long-term Fos expression and hyperalgesia in a model of chronic neuropathic pain. Brain Res. 822:210–219. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Lu Y and Westlund KN: Effects of baclofen on colon inflammation-induced Fos, CGRP and SP expression in spinal cord and brainstem. Brain Res. 889:118–130. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Abbadie C, Besson JM and Calvino B: c-Fos expression in the spinal cord and pain-related symptoms induced by chronic arthritis in the rat are prevented by pretreatment with Freund adjuvant. J Neurosci. 14:5865–5871. 1994.PubMed/NCBI

9 

Hwang HJ, Lee HJ, Kim CJ, Shim I and Hahm DH: Inhibitory effect of amygdalin on lipopolysaccharide-inducible TNF-alpha and IL-1beta mRNA expression and carrageenan-induced rat arthritis. J Microbiol Biotechnol. 18:1641–1647. 2008.PubMed/NCBI

10 

Liu CR, Duan QZ, Wang W, et al: Effects of intrathecal isoflurane administration on nociception and Fos expression in the rat spinal cord. Eur J Anaesthesiol. 28:112–119. 2011. View Article : Google Scholar

11 

Wu J, Hu Q, Huang D, Chen X and Chen J: Effect of electrical stimulation of sciatic nerve on synaptic plasticity of spinal dorsal horn and spinal c-fos expression in neonatal, juvenile and adult rats. Brain Res. 1448:11–19. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Zeng X, Huang H and Hong Y: Effects of intrathecal BAM22 on noxious stimulus-evoked c-fos expression in the rat spinal dorsal horn. Brain Res. 1028:170–179. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Quintero L, Cuesta MC, Silva JA, et al: Repeated swim stress increases pain-induced expression of c-Fos in the rat lumbar cord. Brain Res. 965:259–268. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Terao S, Sobue G, Hashizume Y, Shimada N and Mitsuma T: Age-related changes of the myelinated fibers in the human corticospinal tract: a quantitative analysis. Acta Neuropathol. 88:137–142. 1994. View Article : Google Scholar : PubMed/NCBI

15 

Hukkanen M, Platts LA, Corbett SA, Santavirta S, Polak JM and Konttinen YT: Reciprocal age-related changes in GAP-43/B-50, substance P and calcitonin gene-related peptide (CGRP) expression in rat primary sensory neurones and their terminals in the dorsal horn of the spinal cord and subintima of the knee synovium. Neurosci Res. 42:251–260. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Ranson RN, Priestley DJ, Santer RM and Watson AH: Changes in the substance P-containing innervation of the lumbosacral spinal cord in male Wistar rats as a consequence of ageing. Brain Res. 1036:139–144. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Head E, Nukala VN, Fenoglio KA, Muggenburg BA, Cotman CW and Sullivan PG: Effects of age, dietary, and behavioral enrichment on brain mitochondria in a canine model of human aging. Exp Neurol. 220:171–176. 2009. View Article : Google Scholar : PubMed/NCBI

18 

González-Martínez Á, Rosado B, Pesini P, et al: Plasma β-amyloid peptides in canine aging and cognitive dysfunction as a model of Alzheimer’s disease. Exp Gerontol. 46:590–596. 2011. View Article : Google Scholar

19 

Barańczyk-Kuźma A, Usarek E, Kuźma-Kozakiewcz M, et al: Age-related changes in tau expression in transgenic mouse model of amyotrophic lateral sclerosis. Neurochem Res. 32:415–421. 2007. View Article : Google Scholar

20 

Garbuzova-Davis S, Haller E, Saporta S, Kolomey I, Nicosia SV and Sanberg PR: Ultrastructure of blood-brain barrier and blood-spinal cord barrier in SOD1 mice modeling ALS. Brain Res. 1157:126–137. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Coksaygan T, Magnus T, Cai J, et al: Neurogenesis in Talpha-1 tubulin transgenic mice during development and after injury. Exp Neurol. 197:475–485. 2006. View Article : Google Scholar

22 

Candelario-Jalil E, Alvarez D, Merino N and León OS: Delayed treatment with nimesulide reduces measures of oxidative stress following global ischemic brain injury in gerbils. Neurosci Res. 47:245–253. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Schmued LC and Hopkins KJ: Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration. Brain Res. 874:123–130. 2000. View Article : Google Scholar : PubMed/NCBI

24 

Kendig H, Browning CJ and Young AE: Impacts of illness and disability on the well-being of older people. Disabil Rehabil. 22:15–22. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Thomas E, Peat G, Harris L, Wilkie R and Croft PR: The prevalence of pain and pain interference in a general population of older adults: cross-sectional findings from the North Staffordshire Osteoarthritis Project (NorStOP). Pain. 110:361–368. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Chung JY, Choi JH, Lee CH, et al: Comparison of ionized calcium-binding adapter molecule 1-immunoreactive microglia in the spinal cord between young adult and aged dogs. Neurochem Res. 35:620–627. 2010. View Article : Google Scholar

27 

Ahn JH, Choi JH, Kim JS, et al: Comparison of immunoreactivities in 4-HNE and superoxide dismutases in the cervical and the lumbar spinal cord between adult and aged dogs. Exp Gerontol. 46:703–708. 2011.PubMed/NCBI

28 

Lawrence J, Stroman PW, Bascaramurty S, Jordan LM and Malisza KL: Correlation of functional activation in the rat spinal cord with neuronal activation detected by immunohistochemistry. Neuroimage. 22:1802–1807. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Bullitt E: Expression of c-fos-like protein as a marker for neuronal activity following noxious stimulation in the rat. J Comp Neurol. 296:517–530. 1990. View Article : Google Scholar : PubMed/NCBI

30 

Wu YP and Ling EA: Expression of Fos in the spinal motoneurons labelled by horseradish peroxidase following middle cerebral artery occlusion in rat. Brain Res Bull. 45:571–576. 1998. View Article : Google Scholar : PubMed/NCBI

31 

Kim JM, Lee KW, Chung YH, Shin CM, Baik SH and Cha CI: c-Fos basal immunoreactivity decreases in rat spinal cord during normal ageing. Neuroreport. 10:585–588. 1999. View Article : Google Scholar : PubMed/NCBI

32 

Carballo-Quintás M, Martínez-Silva I, Cadarso-Suárez C, et al: A study of neurotoxic biomarkers, c-fos and GFAP after acute exposure to GSM radiation at 900 MHz in the picrotoxin model of rat brains. Neurotoxicology. 32:478–494. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Sun YN, Luo JY, Rao ZR, Lan L and Duan L: GFAP and Fos immunoreactivity in lumbo-sacral spinal cord and medulla oblongata after chronic colonic inflammation in rats. World J Gastroenterol. 11:4827–4832. 2005.PubMed/NCBI

34 

Hald A, Nedergaard S, Hansen RR, Ding M and Heegaard AM: Differential activation of spinal cord glial cells in murine models of neuropathic and cancer pain. Eur J Pain. 13:138–145. 2009. View Article : Google Scholar

35 

Watkins LR, Milligan ED and Maier SF: Glial activation: a driving force for pathological pain. Trends Neurosci. 24:450–455. 2001. View Article : Google Scholar : PubMed/NCBI

36 

Lee DH, Ahn JH, Park JH, et al: Comparison of expression of inflammatory cytokines in the spinal cord between young adult and aged beagle dogs. Cell Mol Neurobiol. 33:615–624. 2013. View Article : Google Scholar : PubMed/NCBI

37 

Dinapoli VA, Benkovic SA, Li X, et al: Age exaggerates proinflammatory cytokine signaling and truncates signal transducers and activators of transcription 3 signaling following ischemic stroke in the rat. Neuroscience. 170:633–644. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ahn JH, Shin MC, Park JH, Kim IH, Lee JC, Yan BC, Hwang IK, Moon SM, Ahn JY, Ohk TG, Ohk TG, et al: Increased immunoreactivity of c‑Fos in the spinal cord of the aged mouse and dog. Mol Med Rep 11: 1043-1048, 2015.
APA
Ahn, J.H., Shin, M.C., Park, J.H., Kim, I.H., Lee, J., Yan, B.C. ... Won, M. (2015). Increased immunoreactivity of c‑Fos in the spinal cord of the aged mouse and dog. Molecular Medicine Reports, 11, 1043-1048. https://doi.org/10.3892/mmr.2014.2800
MLA
Ahn, J. H., Shin, M. C., Park, J. H., Kim, I. H., Lee, J., Yan, B. C., Hwang, I. K., Moon, S. M., Ahn, J. Y., Ohk, T. G., Lee, T. H., Cho, J. H., Shin, H., Won, M."Increased immunoreactivity of c‑Fos in the spinal cord of the aged mouse and dog". Molecular Medicine Reports 11.2 (2015): 1043-1048.
Chicago
Ahn, J. H., Shin, M. C., Park, J. H., Kim, I. H., Lee, J., Yan, B. C., Hwang, I. K., Moon, S. M., Ahn, J. Y., Ohk, T. G., Lee, T. H., Cho, J. H., Shin, H., Won, M."Increased immunoreactivity of c‑Fos in the spinal cord of the aged mouse and dog". Molecular Medicine Reports 11, no. 2 (2015): 1043-1048. https://doi.org/10.3892/mmr.2014.2800
Copy and paste a formatted citation
x
Spandidos Publications style
Ahn JH, Shin MC, Park JH, Kim IH, Lee JC, Yan BC, Hwang IK, Moon SM, Ahn JY, Ohk TG, Ohk TG, et al: Increased immunoreactivity of c‑Fos in the spinal cord of the aged mouse and dog. Mol Med Rep 11: 1043-1048, 2015.
APA
Ahn, J.H., Shin, M.C., Park, J.H., Kim, I.H., Lee, J., Yan, B.C. ... Won, M. (2015). Increased immunoreactivity of c‑Fos in the spinal cord of the aged mouse and dog. Molecular Medicine Reports, 11, 1043-1048. https://doi.org/10.3892/mmr.2014.2800
MLA
Ahn, J. H., Shin, M. C., Park, J. H., Kim, I. H., Lee, J., Yan, B. C., Hwang, I. K., Moon, S. M., Ahn, J. Y., Ohk, T. G., Lee, T. H., Cho, J. H., Shin, H., Won, M."Increased immunoreactivity of c‑Fos in the spinal cord of the aged mouse and dog". Molecular Medicine Reports 11.2 (2015): 1043-1048.
Chicago
Ahn, J. H., Shin, M. C., Park, J. H., Kim, I. H., Lee, J., Yan, B. C., Hwang, I. K., Moon, S. M., Ahn, J. Y., Ohk, T. G., Lee, T. H., Cho, J. H., Shin, H., Won, M."Increased immunoreactivity of c‑Fos in the spinal cord of the aged mouse and dog". Molecular Medicine Reports 11, no. 2 (2015): 1043-1048. https://doi.org/10.3892/mmr.2014.2800
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