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Octodon degus, a new model to study the agonist and plexus-induced response in the urinary bladder

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Abstract

Urinary bladder function consists in the storage and controlled voiding of urine. Translational studies require animal models that match human characteristics, such as Octodon degus, a diurnal rodent. This study aims to characterize the contractility of the detrusor muscle and the morphology and code of the vesical plexus from O. degus. Body temperature was measured by an intra-abdominal sensor, the contractility of detrusor strips was evaluated by isometric tension recording, and the vesical plexus was studied by electrical field stimulation (EFS) and immunofluorescence. The animals showed a diurnal chronotype as judged from core temperature. The myogenic contractile response of the detrusor muscle to increasing doses of KCl reached its maximum (31.04 mN/mm2) at 60 mM. In the case of cumulative dose–response of bethanecol, the maximum response (37.42 mN/mm2) was reached at 3.2 × 10−4 M. The response to ATP was clearly smaller (3.8 mN/mm2). The pharmacological dissection of the EFS-induced contraction identified ACh and sensory fibers as the main contributors to this response. The neurons of the vesical plexus were located mainly in the trigone area, grouped in big and small ganglia. Out of them, 48.1 % of the neurons were nitrergic and 62.7 % cholinergic. Our results show functional and morphological similarities between the urinary bladder of O. degus and that of humans.

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References

  1. Andersson KE, Arner A (2004) Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev 84:935–986

    Article  CAS  PubMed  Google Scholar 

  2. Arms L, Vizzard MA (2011) Neuropeptides in lower urinary tract function. HandbExpPharmacol:395–423

  3. Asplund R (2005) Nocturia in relation to sleep, health, and medical treatment in the elderly. BJU Int 96(Suppl 1):15–21

    Article  PubMed  Google Scholar 

  4. Baselli EC, Brandes SB, Luthin GR, Ruggieri MR (1999) The effect of pregnancy and contractile activity on bladder muscarinic receptor subtypes. Neurourol Urodyn 18:511–520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Boselli C, Govoni S, Condino AM, D'Agostino G (2001) Bladder instability: a re-appraisal of classical experimental approaches and development of new therapeutic strategies. J Auton Pharmacol 21:219–229

    Article  CAS  PubMed  Google Scholar 

  6. Brading AF, Mostwin JL (1989) Electrical and mechanical responses of guinea-pig bladder muscle to nerve stimulation. BrJPharmacol 98:1083–1090

    CAS  Google Scholar 

  7. Burnstock G (2014) Purinergic signalling in the urinary tract in health and disease. PurinergicSignal 10:103–155

    CAS  Google Scholar 

  8. Canda AE, Chapple CR, Chess-Williams R (2009) Pharmacologic responses of the mouse urinary bladder. Central European Journal of Medicine 4:192–197

    CAS  Google Scholar 

  9. Colonnello V, Iacobucci P, Fuchs T, Newberry RC, Panksepp J (2011) Octodon degus. A useful animal model for social-affective neuroscience research: basic description of separation distress, social attachments and play. NeurosciBiobehavRev 35:1854–1863

    Google Scholar 

  10. Christen R, Thiermann E (1953) Investigation of toxoplasmosis in autochthonous animals of Chile. I. Octodon d. degus (Molina). Boletin de informaciones parasitarias chilenas 8:75–77

    CAS  PubMed  Google Scholar 

  11. Diez-Noguera A (2013) Methods for serial analysis of long time series in the study of biological rhythms. J Circadian Rhythms 11:7

    Article  PubMed  PubMed Central  Google Scholar 

  12. Dixon JS, Gilpin SA, Gilpin CJ, Gosling JA (1983) Intramural ganglia of the human urinary bladder. BrJUrol 55:195–198

    CAS  Google Scholar 

  13. Dixon JS, Jen PY, Gosling JA (2000) The distribution of vesicular acetylcholine transporter in the human male genitourinary organs and its co-localization with neuropeptide Y and nitric oxide synthase. Neurourol Urodyn 19:185–194

    Article  CAS  PubMed  Google Scholar 

  14. Dixon JS, Jen PY, Gosling JA (1997) A double-label immunohistochemical study of intramural ganglia from the human male urinary bladder neck. J Anat 190(Pt 1):125–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ferguson D, Christopher N (1996) Urinary bladder function and drug development. Trends Pharmacol Sci 17:161–165

    Article  CAS  PubMed  Google Scholar 

  16. Fetscher C, Fleichman M, Schmidt M, Krege S, Michel MC (2002) M(3) muscarinic receptors mediate contraction of human urinary bladder. Br J Pharmacol 136:641–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fry CH, Meng E, Young JS (2010) The physiological function of lower urinary tract smooth muscle. AutonNeurosci 154:3–13

    CAS  Google Scholar 

  18. Gabella G (1990) Intramural neurons in the urinary bladder of the guinea-pig. Cell Tissue Res 261:231–237

    Article  CAS  PubMed  Google Scholar 

  19. Gabella G, Uvelius B (1990) Urinary bladder of rat: fine structure of normal and hypertrophic musculature. Cell Tissue Res 262:67–79

    Article  CAS  PubMed  Google Scholar 

  20. Gevaert T, Moles LX, Sagaert X, Libbrecht L, Roskams T, Rorive S, Decaestecker C, Salmon I, De RD (2015) Morphometric and quantitative immunohistochemical analysis of disease-related changes in the upper (suburothelial) lamina propria of the human bladder dome. PLoSOne 10:e0127020

    Article  Google Scholar 

  21. Giglio D, Delbro DS, Tobin G (2005) Postjunctional modulation by muscarinic M2 receptors of responses to electrical field stimulation of rat detrusor muscle preparations. AutonAutacoidPharmacol 25:113–120

    CAS  Google Scholar 

  22. Gilpin CJ, Dixon JS, Gilpin SA, Gosling JA (1983) The fine structure of autonomic neurons in the wall of the human urinary bladder. J Anat 137(Pt 4):705–713

    PubMed  PubMed Central  Google Scholar 

  23. Gomez-Pinilla PJ, Gomez MF, Sward K, Hedlund P, Hellstrand P, Camello PJ, Andersson KE, Pozo MJ (2008) Melatonin restores impaired contractility in aged guinea pig urinary bladder. JPineal Res 44:416–425

    Article  CAS  Google Scholar 

  24. Gomez-Pinilla PJ, Pozo MJ, Camello PJ (2011) Aging differentially modifies agonist-evoked mouse detrusor contraction and calcium signals. Age (Dordr) 33:81–88

    Article  CAS  Google Scholar 

  25. Gomez-Pinilla PJ, Pozo MJ, Camello PJ (2007) Aging impairs neurogenic contraction in guinea pig urinary bladder: role of oxidative stress and melatonin. AmJPhysiol RegulIntegrComp Physiol 293:R793–R803

    CAS  Google Scholar 

  26. Gosling JA, Thompson SA (1977) A neurohistochemical and histological study of peripheral autonomic neurons of the human bladder neck and prostate. Urol Int 32:269–276

    Article  CAS  PubMed  Google Scholar 

  27. Hashitani H, Suzuki H (1995) Electrical and mechanical responses produced by nerve stimulation in detrusor smooth muscle of the guinea-pig. EurJPharmacol 284:177–183

    CAS  Google Scholar 

  28. Hegde SS, Eglen RM (1999) Muscarinic receptor subtypes modulating smooth muscle contractility in the urinary bladder. Life Sci 64:419–428

    Article  CAS  PubMed  Google Scholar 

  29. Hill WG (2015) Control of urinary drainage and voiding. Clinical journal of the American Society of Nephrology : CJASN 10:480–492

    Article  CAS  PubMed  Google Scholar 

  30. Inestrosa NC, Reyes AE, Chacon MA, Cerpa W, Villalon A, Montiel J, Merabachvili G, Aldunate R, Bozinovic F, Aboitiz F (2005) Human-like rodent amyloid-beta-peptide determines Alzheimer pathology in aged wild-type Octodon degu. NeurobiolAging 26:1023–1028

    CAS  Google Scholar 

  31. Kas MJ, Edgar DM (1998) Crepuscular rhythms of EEG sleep-wake in a hystricomorph rodent, Octodon degus. J Biol Rhythm 13:9–17

    Article  CAS  Google Scholar 

  32. Kas MJ, Edgar DM (1999) A nonphotic stimulus inverts the diurnal-nocturnal phase preference in Octodon degus. The Journal of neuroscience : the official journal of the Society for Neuroscience 19:328–333

    CAS  Google Scholar 

  33. Kas MJ, Edgar DM (2001) Scheduled voluntary wheel running activity modulates free-running circadian body temperature rhythms in Octodon degus. J Biol Rhythm 16:66–75

    Article  CAS  Google Scholar 

  34. Kikukawa H, Yoshida M, Wada Y, Nishi K, Ueda S (1998) Pharmacologic actions of temiverine (p-INN) and its active metabolite, RCC-36, on isolated human urinary bladder muscle. International journal of urology : official journal of the Japanese Urological Association 5:268–275

    Article  CAS  Google Scholar 

  35. Koh BH, Roy R, Hollywood MA, Thornbury KD, McHale NG, Sergeant GP, Hatton WJ, Ward SM, Sanders KM, Koh SD (2012) Platelet-derived growth factor receptor-alpha cells in mouse urinary bladder: a new class of interstitial cells. J Cell Mol Med 16:691–700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kujubu DA, Aboseif SR (2008) An overview of nocturia and the syndrome of nocturnal polyuria in the elderly. Nat Clin Pract Nephrol 4:426–435

    Article  PubMed  Google Scholar 

  37. Labyak SE, Lee TM, Goel N (1997) Rhythm chronotypes in a diurnal rodent, Octodon degus. Am J Phys 273:R1058–R1066

    CAS  Google Scholar 

  38. Lee H, Koh BH, Peri LE, Sanders KM, Koh SD (2014) Purinergic inhibitory regulation of murine detrusor muscles mediated by PDGFRalpha+ interstitial cells. J Physiol 592:1283–1293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lee H, Koh BH, Yamasaki E, George NE, Sanders KM, Koh SD (2015) UTP activates small-conductance Ca2+-activated K+ channels in murine detrusor PDGFRalpha+ cells. American journal of physiology Renal physiology 309:F569–F574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Liberti E, De Souza RR, Perito M, Alves N, Chadi G (1994) Number, size and distribution of ganglion neurons in urinary bladder of rodents. Biol Res 27:123–128

    CAS  PubMed  Google Scholar 

  41. Lincoln J, Burnstock G (1993) Autonomic innervation of the urinary bladder and urethra. In: Nervous control of the urogenital system. Harwood Academic Publishers GmbH, Chur, pp. 33–68

    Google Scholar 

  42. Longhurst PA, Leggett RE, Briscoe JA (1995) Characterization of the functional muscarinic receptors in the rat urinary bladder. Br J Pharmacol 116:2279–2285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Malmqvist U, Arner A, Uvelius B (1991) Mechanics and Ca(2+)-sensitivity of human detrusor muscle bundles studied in vitro. Acta Physiol Scand 143:373–380

    Article  CAS  PubMed  Google Scholar 

  44. Mawe GM, Talmage EK, Cornbrooks EB, Gokin AP, Zhang L, Jennings LJ (1997) Innervation of the gallbladder: structure, neurochemical coding, and physiological properties of guinea pig gallbladder ganglia. Microsc Res Tech 39:1–13

    Article  CAS  PubMed  Google Scholar 

  45. Monaghan KP, Johnston L, McCloskey KD (2012) Identification of PDGFRalpha positive populations of interstitial cells in human and guinea pig bladders. JUrol 188:639–647

    CAS  Google Scholar 

  46. Munoz A, Gangitano DA, Smith CP, Boone TB, Somogyi GT (2010) Removal of urothelium affects bladder contractility and release of ATP but not release of NO in rat urinary bladder. BMCUrol 10:10

    Google Scholar 

  47. Neghme A, Rivera G, Tagle I (1956) Attempted experimental infection of Octodon degus degus, Molina with Echinococcus granulosis. Boletin chileno de parasitologia 11:33–34

    CAS  PubMed  Google Scholar 

  48. Negoro H, Kanematsu A, Yoshimura K, Ogawa O (2013) Chronobiology of micturition: putative role of the circadian clock. JUrol 190:843–849

    Google Scholar 

  49. Ocampo-Garces A, Hernandez F, Mena W, Palacios AG (2005) Wheel-running and rest activity pattern interaction in two octodontids (Octodon degus, Octodon bridgesi). Biol Res 38:299–305

    Article  PubMed  Google Scholar 

  50. Ochodnicky P, Uvelius B, Andersson KE, Michel MC (2013) Autonomic nervous control of the urinary bladder. Acta Physiol 207:16–33

    Article  CAS  Google Scholar 

  51. Persson K, Alm P, Johansson K, Larsson B, Andersson KE (1993) Nitric oxide synthase in pig lower urinary tract: immunohistochemistry, NADPH diaphorase histochemistry and functional effects. Br J Pharmacol 110:521–530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Persson K, Andersson KE (1992) Nitric oxide and relaxation of pig lower urinary tract. Br J Pharmacol 106:416–422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Pessina F, Marazova K, Kalfin R, Sgaragli G, Manganelli A, Milenov K (2001) Mechanical response to electrical field stimulation of rat, guinea-pig, monkey and human detrusor muscle: a comparative study. Naunyn Schmiedeberg's Arch Pharmacol 363:543–550

    Article  CAS  Google Scholar 

  54. Ramos-Filho AC, Monica FZ, Franco-Penteado CF, Rojas-Moscoso JA, Bau FR, Schenka AA, De NG, Antunes E (2011) Characterization of the urinary bladder dysfunction in renovascular hypertensive rats. Neurourol Urodyn 30:1392–1402

    PubMed  Google Scholar 

  55. Ramos-Filho AC, Shah A, Augusto TM, Barbosa GO, Leiria LO, de Carvalho HF, Antunes E, Grant AD (2014) Menthol inhibits detrusor contractility independently of TRPM8 activation. PLoS One 9:e111616

    Article  PubMed  PubMed Central  Google Scholar 

  56. Sagawa K, Aikawa K, Nomiya M, Ogawa S, Akaihata H, Takahashi N, Yamaguchi O, Kojima Y (2013) Impaired detrusor contractility in a rat model of chronic bladder ischemia. Urology 81:1379–1314

    Article  PubMed  Google Scholar 

  57. Saito M, Kondo A, Gotoh M, Kato K (1991) Age-related changes in the rat detrusor muscle: the contractile response to inorganic ions. J Urol 146:891–894

    CAS  PubMed  Google Scholar 

  58. Schmid B, Helfrich-Forster C, Yoshii T (2011) A new ImageJ plug-in "ActogramJ" for chronobiological analyses. J Biol Rhythm 26:464–467

    Article  Google Scholar 

  59. Schneider T, Fetscher C, Krege S, Michel MC (2004) Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther 309:1148–1153

    Article  CAS  PubMed  Google Scholar 

  60. Sellers DJ, Chess-Williams R (2012) Muscarinic agonists and antagonists: effects on the urinary bladder. Handb Exp Pharmacol:375–400

  61. Sibley GN (1984) A comparison of spontaneous and nerve-mediated activity in bladder muscle from man, pig and rabbit. J Physiol 354:431–443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Smet PJ, Edyvane KA, Jonavicius J, Marshall VR (1996) Neuropeptides and neurotransmitter-synthesizing enzymes in intrinsic neurons of the human urinary bladder. J Neurocytol 25:112–124

    Article  CAS  PubMed  Google Scholar 

  63. Smet PJ, Jonavicius J, Marshall VR, de Vente J (1996) Distribution of nitric oxide synthase-immunoreactive nerves and identification of the cellular targets of nitric oxide in guinea-pig and human urinary bladder by cGMP immunohistochemistry. Neuroscience 71:337–348

    Article  CAS  PubMed  Google Scholar 

  64. Vivanco P, Lopez-Espinoza A, Madariaga AM, Rol MA, Madrid JA (2010) Nocturnalism induced by scheduled feeding in diurnal Octodon degus. Chronobiol Int 27:233–250

    Article  PubMed  Google Scholar 

  65. Vivanco P, Rol MA, Madrid JA (2010) Temperature cycles trigger nocturnalism in the diurnal homeotherm Octodon degus. Chronobiol Int 27:517–534

    Article  PubMed  Google Scholar 

  66. Wang P, Luthin GR, Ruggieri MR (1995) Muscarinic acetylcholine receptor subtypes mediating urinary bladder contractility and coupling to GTP binding proteins. J Pharmacol Exp Ther 273:959–966

    CAS  PubMed  PubMed Central  Google Scholar 

  67. White RS, Zemen BG, Khan Z, Montgomery JR, Herrera GM, Meredith AL (2014) Evaluation of mouse urinary bladder smooth muscle for diurnal differences in contractile properties. Front Pharmacol 5:293

    PubMed  Google Scholar 

  68. Yamanishi T, Chapple CR, Yasuda K, Chess-Williams R (2000) The role of M(2)-muscarinic receptors in mediating contraction of the pig urinary bladder in vitro. Br J Pharmacol 131:1482–1488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Yamanishi T, Kaga K, Fuse M, Shibata C, Kamai T, Uchiyama T (2015) The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia. J Pharmacol Sci 128:65–70

    Article  CAS  PubMed  Google Scholar 

  70. Yokoyama O, Miwa Y, Oyama N, Aoki Y, Ito H, Tanase K, Ishida H, Matsuta Y, Kusukawa N, Yamauchi H et al (2011) Urethral sensations are related to the development of detrusor overactivity. Lower urinary tract symptoms 3:59–63

    Article  PubMed  Google Scholar 

  71. Yono M, Yoshida M, Takahashi W, Inadome A, Ueda S (2000) Comparison of the effects of novel antimuscarinic drugs on human detrusor smooth muscle. BJU Int 86:719–725

    Article  CAS  PubMed  Google Scholar 

  72. Yono M, Yoshida M, Wada Y, Kikukawa H, Takahashi W, Inadome A, Seshita H, Ueda S (1999) Pharmacological effects of tolterodine on human isolated urinary bladder. Eur J Pharmacol 368:223–230

    Article  CAS  PubMed  Google Scholar 

  73. Yoshida M, Homma Y, Inadome A, Yono M, Seshita H, Miyamoto Y, Murakami S, Kawabe K, Ueda S (2001) Age-related changes in cholinergic and purinergic neurotransmission in human isolated bladder smooth muscles. Exp Gerontol 36:99–109

    Article  CAS  PubMed  Google Scholar 

  74. Zhang X, Kuppam DS, Melman A, DiSanto ME (2011) In vitro and in vivo relaxation of urinary bladder smooth muscle by the selective myosin II inhibitor, blebbistatin. BJUInt 107:310–317

    Article  CAS  Google Scholar 

  75. Zhou Y, Ling EA (1998) Colocalization of nitric oxide synthase and some neurotransmitters in the intramural ganglia of the guinea pig urinary bladder. J Comp Neurol 394:496–505

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors cordially thank the technician Fatima Barriga for their valuable assistance. This study was supported by Ministerio de Ciencia e Innovación, Spain (BFU2011-24365); Red Temática de Investigación en Envejecimiento y Fragilidad (RETICEF RD12/0043/0016, RD12/0043/0011; RD12/0043/0022); Fondo Europeo de Desarrollo Regional (FEDER); and Junta de Extremadura, Spain (GR10009).

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Correspondence to Maria Jose Pozo.

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All experimental protocols were approved by the ethics committee of the University of Extremadura, following the International Guiding Principles for Biomedical Research Involving Animals.

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Martin-Cano, F.E., Caso-Agundez, M., Camello-Almaraz, C. et al. Octodon degus, a new model to study the agonist and plexus-induced response in the urinary bladder. J Physiol Biochem 73, 77–87 (2017). https://doi.org/10.1007/s13105-016-0527-z

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