Skip to main content
SpringerLink
Log in

Escitalopram affects spexin expression in the rat hypothalamus, hippocampus and striatum

  • Original article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Background

Spexin (SPX) is a recently discovered neuropeptide that exhibits a large spectrum of central and peripheral regulatory activity, especially when considered as a potent anorexigenic factor. It has already been proven that antidepressants, including selective serotonin reuptake inhibitors (SSRI), can modulate peptidergic signaling in various brain structures. Despite these findings, there is so far no information regarding the influence of treatment with the SSRI antidepressant escitalopram on brain SPX expression.

Methods

In this current study we measured SPX mRNA and protein expression in the selected brain structures (hypothalamus, hippocampus and striatum) of rats chronically treated with a 10 mg/kg dose of escitalopram using quantitative Real-Time PCR and immunohistochemistry.

Results

Strikingly, long-term (4 week) drug treatment led to the downregulation of SPX expression in the rat hypothalamus. This supports the hypothesis that SPX may be involved in the hypothalamic serotonin-dependent actions of SSRI antidepressants and possibly also in the central mechanism of body mass increase. Conversely, SPX expression increased in the hippocampus and striatum.

Conclusions

This is the first report of the effects of a neuropsychiatric medication on SPX expression in animal brain. Our findings shed a new light on the pharmacology of antidepressants and may contribute to a better understanding of the alternative mechanisms responsible for antidepressant action.

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

Similar content being viewed by others

References

  1. Lyu RM, Huang XF, Zhang Y, Dun SL, Luo JJ, Chang JK, et al. Phoenixin: a novel peptide in rodent sensory ganglia. Neuroscience 2013;250:622–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Pałasz A, Krzystanek M, Worthington J, Czajkowska B, Kostro K, Wiaderkiewicz R, et al. Nesfatin-1, a unique regulatory neuropeptide of the brain. Neuropeptides 2012;46(3):105–12.

    Article  PubMed  CAS  Google Scholar 

  3. Yosten GL, Lyu RM, Hsueh AJ, Avsian-Kretchmer O, Chang JK, Tullock CW, et al. A novel reproductive peptide, phoenixin. J Neuroendocrinol 2013;25(2):206–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mirabeau O, Perlas E, Severini C, Audero E, Gascuel O, Possenti R, et al. Identification of novel peptide hormones in the human proteome by hidden Markov model screening. Genome Res 2007;17(3):320–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Porzionato A, Rucinski M, Macchi V, Stecco C, Sarasin G, Sfriso MM, et al. Spexin is expressed in the carotid body and is upregulated by postnatal hyperoxia exposure. Adv Exp Med Biol 2012;758:207–13.

    Article  CAS  PubMed  Google Scholar 

  6. Porzionato A, Rucinski M, Macchi V, Stecco C, Malendowicz LK, De Caro R. Spexin expression in normal rat tissues. J Histochem Cytochem 2010;58(9):825–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wong MK, Sze KH, Chen T, Cho CK, Law HC, Chu IK, et al. Goldfish spexin: solution structure and novel function as a satiety factor in feeding control. Am J Physiol Endocrinol Metab 2013;305(3):E348–66.

    Article  CAS  PubMed  Google Scholar 

  8. Li S, Liu Q, Xiao L, Chen H, Li G, Zhang Y, et al. Molecular cloning and functional characterization of spexin in orange-spotted grouper (Epinephelus coioides). Comp Biochem Physiol B Biochem Mol Biol 2016; 196-197:85–91.

    Article  CAS  Google Scholar 

  9. Walewski JL, Ge F, Lobdell HT, Levin N, Schwartz GJ, Vasselli JR, et al. Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet-induced obesity. Obesity (Silver Spring) 2014;22(7):1643–52.

    Article  CAS  Google Scholar 

  10. Walewski JL, Ge F, Gagner M, Inabnet WB, Pomp A, Branch AD, et al. Adipocyte accumulation of long-chain fatty acids in obesity is multifactorial, resulting from increased fatty acid uptake and decreased activity of genes involved in fat utilization. Obes Surg 2010;20(1):93–107.

    Article  PubMed  Google Scholar 

  11. Toll L, Khroyan TV, Sonmez K, Ozawa A, Lindberg I, McLaughlin JP, et al. Peptides derived from the prohormone proNPQ/spexin are potent central modulators of cardiovascular and renal function and nociception. FASEB J 2012;26(2):947–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rucinski M, Porzionato A, Ziolkowska A, Szyszka M, Macchi V, De Caro R, et al. Expression of the spexin gene in the rat adrenal gland and evidences suggesting that spexin inhibits adrenocortical cell proliferation. Peptides 2010;31(4):676–82.

    Article  CAS  PubMed  Google Scholar 

  13. Kim DK, Yun S, Son GH, Hwang JI, Park CR, Kim JI, et al. Coevolution of the spexin/galanin/kisspeptin family: spexin activates galanin receptor type II and III. Endocrinology 2014;155(5):1864–73.

    Article  PubMed  CAS  Google Scholar 

  14. Reyes-Alcaraz A, Lee YN, Son GH, Kim NH, Kim DK, Yun S, et al. Development of spexin-based human galanin receptor type II-specific agonists with increased stability in serum and anxiolytic effect in mice. Sci Rep 2016;24(6):1–10.

    Google Scholar 

  15. Lin CY, Zhang M, Huang T, Yang LL, Fu HB, Zhao L, et al. Spexin enhances bowel movement through activating L-type voltage-dependent calcium channel via galanin receptor 2 in mice. Sci Rep 2015;10(5):1–12.

    Google Scholar 

  16. Owens MJ, Knight DL, Nemeroff CB. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol Psychiatry 2001;50(5):345–50.

    Article  CAS  PubMed  Google Scholar 

  17. Deshmukh R, Franco K. Managing weight gain as a side effect of antidepressant therapy. Clevel Clin J Med 2003;70(7)614 616, 618, passim.

    Article  Google Scholar 

  18. Ranjbar S, Pai N, Deng C. The association of antidepressant medication and body weight gain. Online J Health Allied Sci 2013;12:1–9.

    Google Scholar 

  19. Flandreau EI, Bourke CH, Ressler KJ, Vale WW, Nemeroff CB, Owens MJ. Escitalopram alters gene expression and HPA axis reactivity in rats following chronic overexpression of corticotropin-releasing factor from the central amygdala. Psychoneuroendocrinology 2013;38(8):1349–61.

    Article  CAS  PubMed  Google Scholar 

  20. Schule C. Neuroendocrinological mechanisms of actions of antidepressant drugs. J Neuroendocrinol 2007;19(3):213–26.

    Article  CAS  PubMed  Google Scholar 

  21. Nothdurfter C, Schmotz C, Sarubin N, Baghai TC, Laenger A, Lieb M, et al. Effects of escitalopram/quetiapine combination therapy versus escitalopram monotherapy on hypothalamic-pituitary-adrenal-axis activity in relation to antidepressant effectiveness. J Psychiatr Res 2014;52:15–20.

    Article  PubMed  Google Scholar 

  22. Sattin A, Pekary AE, Blood J. Escitalopram regulates expression of TRH and TRH-like peptides in rat brain and peripheral tissues. Neuroendocrinology 2008;88(2):135–46.

    Article  CAS  PubMed  Google Scholar 

  23. Buhl ES, Jensen TK, Jessen N, Elfving B, Buhl CS, Kristiansen SB, et al. Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats. Am J Physiol Endocrinol Metab 2010;298(May (5)):E920–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kumar S, Hossain J, Nader N, Aguirre R, Sriram S, Balagopal PB. Decreased circulating levels of spexin in obese children. J Clin Endocrinol Metab 2016; (May 24):jc20161177.

    Google Scholar 

  25. Uguz F, Sahingoz M, Gungor B, Aksoy F, Askin R. Weight gain and associated factors in patients using newer antidepressant drugs. Gen Hosp Psychiatry 2015;37(1):46–8.

    Article  PubMed  Google Scholar 

  26. Uher R, Mors O, Hauser J, Rietschel M, Maier W, Kozel D, et al. Changes in body weight during pharmacological treatment of depression. Int J Neuropsychopharmacol 2011;14(3):367–75.

    Article  PubMed  Google Scholar 

  27. Krasnow SM, Fraley GS, Schuh SM, Baumgartner JW, Clifton DK, Steiner RA. A role for galanin-like peptide in the integration of feeding, body weight regulation, and reproduction in the mouse. Endocrinology 2003;144:813–22.

    Article  CAS  PubMed  Google Scholar 

  28. Shiba K, Kageyama H, Takenoya F, Shioda S. Galanin-like peptide and the regulation of feeding behavior and energy metabolism. FEBS J 2010;277(24):5006–13.

    Article  CAS  PubMed  Google Scholar 

  29. Lawrence CB, Williams T, Luckman SM. Intracerebroventricular galanin-like peptide induces different brain activation compared with galanin. Endocrinology 2003;144:3977–84.

    Article  CAS  PubMed  Google Scholar 

  30. Katai Z, Adori C, Kitka T, Vas S, Kalmar L, Kostyalik D, et al. Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH-expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation. Psychopharmacology (Berl) 2013;228(3):439–49.

    Article  CAS  Google Scholar 

  31. Ozsoy S, Olguner Eker O, Abdulrezzak U. The effects of antidepressants on neuropeptide Y in patients with depression and anxiety. Pharmacopsychiatry 2016;49(1):26–31.

    Article  CAS  PubMed  Google Scholar 

  32. Marais L, Hattingh SM, Stein DJ, Daniels WM. A proteomic analysis of the ventral hippocampus of rats subjected to maternal separation and escitalopram treatment. Metab Brain Dis 2009;24(4):569–86.

    Article  CAS  PubMed  Google Scholar 

  33. Hui J, Zhang Z, Liu S, Xi G, Zhang X, Teng G, et al. Adolescent escitalopram administration modifies neurochemical alterations in the hippocampus of maternally separated rats. Eur Neuropsychopharmacol 2010;20(12):875–83.

    Article  CAS  PubMed  Google Scholar 

  34. Jayatissa MN, Bisgaard CF, West MJ, Wiborg O. The number of granule cells in rat hippocampus is reduced after chronic mild stress and reestablished after chronic escitalopram treatment. Neuropharmacology 2008;54(3):530–41.

    Article  CAS  PubMed  Google Scholar 

  35. Hovelso N, Sager TN, Mork A. Combination of escitalopram and a 5-HT((1)A) receptor antagonist selectively decreases the extracellular levels of dopamine in the nucleus accumbens relative to striatum through 5-HT((2)C) receptor stimulation; suggestive of antipsychotic potential. Pharmacol Biochem Behav 2011;97(3):479–85.

    Article  CAS  PubMed  Google Scholar 

  36. Lu X, Barr AM, Kinney JW, Sanna P, Conti B, Behrens MM, et al. A role for galanin in antidepressant actions with a focus on the dorsal raphe nucleus. Proc Natl Acad Sci U S A 2005;102(3):874–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Petschner P, Juhasz G, Tamasi V, Adori C, Tothfalusi L, Hökfelt T, et al. Chronic venlafaxine treatment fails to alter the levels of galanin system transcripts in normal rats. Neuropeptides 2016;57:65–70.

    Article  CAS  PubMed  Google Scholar 

  38. Castren E. Is mood chemistry? Nat Rev Neurosci 2005;6(3):241–6.

    Article  CAS  PubMed  Google Scholar 

  39. Tamasi V, Petschner P, Adori C, Kirilly E, Ando RD, Tothfalusi L, et al. Transcriptional evidence for the role of chronic venlafaxine treatment in neurotrophic signaling and neuroplasticity including also Glutamatergic [corrected] — and insulin-mediated neuronal processes. PLoS One 2014;9(11):e11366.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Histology, School of Medicine in Katowice, Medical University of Silesia, Medyków 18, Katowice, 40-752, Poland

    Artur Pałasz, Aleksandra Suszka-Świtek, Łukasz Filipczyk, Katarzyna Bogus, Ewa Rojczyk & Ryszard Wiaderkiewicz

  2. Manchester Immunology Group, Faculty of Life Sciences, University of Manchester, Greater Manchester, M13 9PT, UK

    John Worthington

  3. Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YQ, UK

    John Worthington

  4. Department and Clinic of Psychiatric Rehabilitation, School of Medicine in Katowice, Medical University of Silesia, Ziolowa 45/47, Katowice, 40-635, Poland

    Marek Krzystanek

Authors
  1. Artur Pałasz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aleksandra Suszka-Świtek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Łukasz Filipczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katarzyna Bogus
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ewa Rojczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John Worthington
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marek Krzystanek
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ryszard Wiaderkiewicz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Artur Pałasz.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pałasz, A., Suszka-Świtek, A., Filipczyk, Ł. et al. Escitalopram affects spexin expression in the rat hypothalamus, hippocampus and striatum. Pharmacol. Rep 68, 1326–1331 (2016). https://doi.org/10.1016/j.pharep.2016.09.002

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.pharep.2016.09.002

Keywords

Search

Navigation