Skip to main content

Advertisement

Log in

Corticotropin-releasing factor (CRF) expression in postnatal and adult rat sacral parasympathetic nucleus (SPN)

  • Regular article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The neural control of micturition undergoes marked changes during the early postnatal development. During the first few postnatal weeks, the spinal micturition reflex is gradually replaced by a spinobulbospinal reflex pathway that is responsible for micturition in adult animals. Upregulation of brainstem regulation of spinal micturition pathways may contribute to development of mature voiding patterns. We examined the expression of corticotropin-releasing factor (CRF), present in descending projections from Barrington's nucleus to the sacral parasympathetic nucleus (SPN), in postnatal (P0–P36) and adult Wistar rats (P60–90). CRF-immunoreactivity (IR) was present predominantly in the SPN region, although some staining was also observed in the dorsal horn and dorsal commissure in L5–S1 spinal segments. CRF-IR in spinal cord regions was age dependent (R 2=0.87–0.98). The majority of the CRF-IR in the lumbosacral spinal cord was eliminated by complete spinalization (2–3 weeks). Double-label immunohistochemistry was combined with quantitative confocal laser scanning microscopy to quantify the number and percentage of colocalization between CRF-immunoreactive varicosities and preganglionic somas or proximal neurites in the SPN in postnatal and adult rats. Results demonstrate an age-dependent upregulation of CRF-IR in the SPN region and specifically in association with preganglionic parasympathetic neurons identified with neuronal nitric oxide synthase (nNOS)-IR. CRF-immunoreactive varicosities on or within a 1 μm perimeter of nNOS-immunoreactive somas or proximal neurites also increased with postnatal age. The upregulation of CRF-IR in bulbospinal projections to the SPN may contribute to mature voiding reflexes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Araki I, de Groat WC (1996) Unitary excitatory synaptic currents in preganglionic neurons mediated by two distinct groups of interneurons in neonatal rat sacral parasympathetic nucleus. J Neurophysiol 76:215–226

    PubMed  CAS  Google Scholar 

  • Araki I, de Groat WC (1997) Developmental synaptic depression underlying reorganization of visceral reflex pathways in the spinal cord. J Neurosci 17:8402–8407

    PubMed  CAS  Google Scholar 

  • Bregman BS (1987) Development of serotonin immunoreactivity in the rat spinal cord and its plasticity after neonatal spinal cord lesions. Dev Brain Res 34:245–263

    Article  Google Scholar 

  • Capek K, Jelinek J (1956) The development of the control of water metabolism. I. The excretion of urine in young rats. Physiol Bohemoslov 5:91–96

    PubMed  CAS  Google Scholar 

  • de Groat WC (1975) Nervous control of the urinary bladder of the cat. Brain Res 87:201–211

    Article  PubMed  Google Scholar 

  • de Groat WC, Kruse MN (1993) Central processing and morphological plasticity in lumbosacral afferent pathways from the lower urinary tract. In: Mayer EA, Raybould HE (eds) Basic and clinical aspects of chronic abdominal painain research and clinical management. Elsevier, Amsterdam pp 219–235

    Google Scholar 

  • de Groat WC, Araki I (1999) Maturation of bladder reflex pathways during postnatal development. Adv Exp Med Biol 462:253–263; discussion 311–220

    PubMed  Google Scholar 

  • de Groat WC, Nadelhaft I, Milne RJ, Booth AM, Morgan C, Thor K (1981) Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine. J Auton Nerv Syst 3:135–160

    Article  PubMed  Google Scholar 

  • de Groat WC, Kawatani M, Hisamitsu T, Cheng C-L, Ma C-P, Thor K, Steers W, Roppolo JR (1990) Mechanisms underlying the recovery of urinary bladder function following spinal cord injury. J Auton Nerv Syst 30:571–578

    Google Scholar 

  • de Groat WC, Booth AM, Yoshimura N (1993) Neurophysiology of micturition and its modification in animal models of human disease. In: Maggi CA (ed) The autonomic nervous system. Harwood, London, pp 227–290

    Google Scholar 

  • de Groat WC, Kruse MN, Vizzard MA, Cheng C-L, Araki I, Yoshimura N (1997) Modification of urinary bladder function after spinal cord injury. In: Seil FJ (ed) Advances in neurology. Raven, New York, pp 347–364

    Google Scholar 

  • de Groat WC, Araki I, Vizzard MA, Yoshiyama M, Yoshimura N, Sugaya K, Tai C, Roppolo JR (1998) Developmental and injury induced plasticity in the micturition reflex pathway. Behav Brain Res 92(2):127–140

    Article  PubMed  Google Scholar 

  • Fitzgerald M (1991) Development of pain mechanisms. Br Med Bull 47:667–675

    PubMed  CAS  Google Scholar 

  • Ginsberg SD, Hof PR, Young WG, Morrison JH (1994) Noradrenergic innervation of vasopressin-and oxytocin-containing neurons in the hypothalamic paraventricular nucleus of the macaque monkey: quantitative analysis using double-label immunohistochemistry and confocal laser microscopy. J Comp Neurol 341(4):476–491

    Article  PubMed  CAS  Google Scholar 

  • Goodman CS, Shatz CJ (1993) Developmental mechanisms that generate precise patterns of neuronal connectivity. Cell 72(Suppl):77–98

    Article  PubMed  Google Scholar 

  • Johnson JM, Skau KA, Gerald MC, Wallace LJ (1988) Regional noradrenergic and cholinergic neurochemistry in the rat urinary bladder: effect of age. J Urol 139:611–615

    PubMed  CAS  Google Scholar 

  • Klausner AP, Steers WD (2004) Corticotropin releasing factor: a mediator of emotional influences on bladder function. J Urol 172(6 Pt 2):2570–2573

    Article  PubMed  CAS  Google Scholar 

  • Kruse MN, Tanowitz M, Cheng C, de Groat WC (1990) Postnatal development of the sensory innervation of the urinary bladder in the rat. Soc Neurosci Abstr 16:1064

    Google Scholar 

  • Loewy AD, Saper CB, Baker RP (1979) Descending projections from the pontine micturition center. Brain Res 172:533–538

    Article  PubMed  CAS  Google Scholar 

  • Maggi CA, Santicioli P, Geppeti S, Frilli MG, Spillantini MG, Nediani C, Hunt SP, Meli A (1988) Biochemical, anatomical and functional correlates of postnatal developments of the capsaicin-sensitive innervation of the rat urinary bladder. Dev Brain Res 43:183–190

    Article  CAS  Google Scholar 

  • Malley S, Haas DY, Zvarova K, Zvara P, Vizzard MA (2003) Reciprocal relationship between corticotropin-releasing hormone (DRH) immunoreactivity (IR) and perineal afferent projections in the rat lumbosacral spinal cord during postnatal development. Abstract Viewer/Itinerary Planner Program number 608.13 (Society for Neuroscience, Washington D.C.)

  • Marson L (1997) Identification of central nervous system neurons that innervate the bladder body, bladder base, or external urethral sphincter of female rats: a transneuronal tracing study using pseudorabies virus. J Comp Neurol 389(4):584–602

    Article  PubMed  CAS  Google Scholar 

  • Marson L, Platt KB, McKenna KE (1993) Central nervous system innervation of the penis as revealed by the transneuronal transport of pseudorabies virus. Neuroscience 55(1):263–280

    Article  PubMed  CAS  Google Scholar 

  • Marti E, Gibson SJ, Polak JM, Facer P, Springall DR, Van Aswegen G, Aithison M, Koltzenburg M (1987) Ontogeny of peptide and amine containing neurones in motor, sensory, and autonomic regions of rat and human spinal cord, dorsal root ganglia and rat skin. J Comp Neurol 266:332–359

    Article  PubMed  CAS  Google Scholar 

  • Merchenthaler I (1984) Corticotropin releasing factor (CRF)-like immunoreactivity in the rat central nervous system. Extrahypothalamic distribution. Peptides 5:53–69

    Article  PubMed  CAS  Google Scholar 

  • Merchenthaler I, Vigh S, Petrusz P, Schally AV (1982) Immunocytochemical localization of corticotropin releasing factor (CRF) in the rat brain. Am J Anat 165:385–396

    Article  PubMed  CAS  Google Scholar 

  • Morgan C, Nadelhaft I, de Groat WC (1981) The distribution of visceral primary afferents from the pelvic nerve within Lissauer's tract and the spinal gray matter and its relationship to the sacral parasympathetic nucleus. J Comp Neurol 201:415–440

    Article  PubMed  CAS  Google Scholar 

  • Nadelhaft I, Vera PL (1995) Central nervous system neurons infected by pseudorabies virus injected into the rat urinary bladder following unilateral transection of the pelvic nerve. J Comp Neurol 359:443–456

    Article  PubMed  CAS  Google Scholar 

  • Noto H, Roppolo JR, Steers WD, de Groat WC (1989) Excitatory and inhibitory influences on bladder activity elicited by electrical stimulation in the pontine micturition center in the rat. Brain Res 492(1–2):99–115

    Article  PubMed  CAS  Google Scholar 

  • Pavcovich LA, Yang M, Miselis RR, Valentino RJ (1998) Novel role for the pontine micturition center, Barrington's nucleus: evidence for coordination of colonic and forebrain activity. Brain Res 784(1–2):355–361

    Article  PubMed  CAS  Google Scholar 

  • Puder BA, Papka RE (2001) Distribution and origin of corticotropin-releasing factor-immunoreactive axons in the female rat lumbosacral spinal cord. J Neurosci Res 66(6):1217–1225

    Article  PubMed  CAS  Google Scholar 

  • Rouzade-Dominguez ML, Pernar L, Beck S, Valentino RJ (2003) Convergent responses of Barrington's nucleus neurons to pelvic visceral stimuli in the rat: a juxtacellular labelling study. Eur J Neurosci 18(12):3325–3334

    Article  PubMed  Google Scholar 

  • Saban MR, Nguyen NB, Hammond TG, Saban R (2002) Gene expression profiling of mouse bladder inflammatory responses to LPS, substance P, and antigen-stimulation. Am J Pathol 160(6):2095–2110

    PubMed  CAS  Google Scholar 

  • Satoh K, Shimizu N, Tohyama M, Maeda T (1978) Localization of the micturition reflex center at dorsolateral pontine tegmentum of the rat. Neurosci Lett 8:27–33

    Article  Google Scholar 

  • Skofitsch G, Hamill GS, Jacobowitz DM (1984) Capsaicin depletes corticotropin-releasing factor-like immunoreactive neurons in the rat spinal cord and medulla oblongata. Neuroendocrinology 38(6):514–517

    PubMed  CAS  Google Scholar 

  • Steers WD, de Groat WC (1988) Effect of bladder outlet obstruction on micturition reflex pathways in the rat. J Urol 140:864–871

    PubMed  CAS  Google Scholar 

  • Steers WD, Ciambotti J, Etzel B, Erdman S, de Groat WC (1991) Alterations in afferent pathways from the urinary bladder of the rat in response to partial urethral obstruction. J Comp Neurol 310:1–10

    Article  PubMed  Google Scholar 

  • Steers WD, Creedon DJ, Tuttle JB (1996) Immunity to nerve growth factor prevents afferent plasticity following urinary bladder hypertrophy. J Urol 155:379–385

    Article  PubMed  CAS  Google Scholar 

  • Sugaya K, Roppolo JR, Yoshimura N, Card JP, de Groat WC (1997) The central neural pathways involved in micturition in the neonatal rat as revealed by the injection of pseudorabies virus into the urinary bladder. Neurosci Lett 223(3):197–200

    Article  PubMed  CAS  Google Scholar 

  • Suzuki T, Kawatani M, Erdman S, de Groat WC (1990) Role of CRF and 5-HT in central pathways controlling micturition in the rat. Soc Neurosci Abstr 16:1064

    Google Scholar 

  • Thor KB, Kawatani M, de Groat WC (1986) Plasticity in the reflex pathways to the lower urinary tract of the cat during postnatal development and following spinal injury. In: Goldberger ME, Gorio A, Murray M (eds) Development and plasticity of the mammalian spinal cord. Liviana, Padova, pp 65–81

    Google Scholar 

  • Thor KB, Blais DP, de Groat WC (1989) Behavioral analysis of the postnatal development of micturition in kittens. Dev Brain Res 46:137–144

    Article  CAS  Google Scholar 

  • Thor KB, Hisamitsu T, de Groat WC (1990) Unmasking of a neonatal somatovesical reflex in adult cats by the serotonin autoreceptor agonist 5-methoxy-N,N-dimethyltryptamine. Dev Brain Res 54:35–42

    Article  CAS  Google Scholar 

  • Todd AJ, Puskar Z, Spike RC, Hughes C, Watt C, Forrest L (2002) Projection neurons in lamina I of rat spinal cord with the neurokinin 1 receptor are selectively innervated by substance P-containing afferents and respond to noxious stimulation. J Neurosci 22(10):4103–4113

    PubMed  CAS  Google Scholar 

  • Valentino RJ, Pavcovich LA, Hirata H (1995) Evidence for corticotropin-releasing hormone projections from Barrington's nucleus to the periaqueductal gray and dorsal motor nucleus of the vagus in the rat. J Comp Neurol 363(3):402–422

    Article  PubMed  CAS  Google Scholar 

  • Valentino RJ, Chen S, Zhu Y, Aston-Jones G (1996) Evidence for divergent projections to the brain noradrenergic system and the spinal parasympathetic system from Barrington's nucleus. Brain Res 732(1–2):1–15

    Article  PubMed  CAS  Google Scholar 

  • Vincent SR, Satoh K (1984) Corticotropin-releasing factor (CRF) immunoreactivity in the dorsolateral pontine tegmentum: further studies on the micturition reflex system. Brain Res 308:387–391

    Article  PubMed  CAS  Google Scholar 

  • Vizzard MA (1997) Increased expression of neuronal nitric oxide synthase in bladder afferent and spinal neurons following spinal cord injury. Dev Neurosci 19(3):232–246

    Article  PubMed  CAS  Google Scholar 

  • Vizzard MA (1999) Alterations in growth-associated protein (GAP-43) expression in lower urinary tract pathways following chronic spinal cord injury. Somatosen Motor Res 16(4):369–381

    Article  CAS  Google Scholar 

  • Vizzard MA (2000) Up-regulation of pituitary adenylate cyclase-activating polypeptide in urinary bladder pathways after chronic cystitis. J Comp Neurol 420(3):335–348

    Article  PubMed  CAS  Google Scholar 

  • Vizzard MA, Erdman SL, Forstermann U, de Groat WC (1994) Ontogeny of nitric oxide synthase in the lumbosacral spinal cord of the neonatal rat. Dev Brain Res 81:201–217

    Article  CAS  Google Scholar 

  • Vizzard MA, Erdman SL, de Groat WC (1995) Increased expression of neuronal nitric oxide synthase (NOS) in visceral neurons after nerve injury. J Neurosci 15(5):4033–4045

    PubMed  CAS  Google Scholar 

  • Vizzard MA, Brisson M, de Groat WC (2000a) Transneuronal labeling of neurons in the adult rat central nervous system following inoculation of pseudorabies virus into the colon. Cell Tissue Res 299(1):9–26

    Article  PubMed  CAS  Google Scholar 

  • Vizzard MA, Wu KH, Jewett IT (2000b) Developmental expression of urinary bladder neurotrophic factor mRNA and protein in the neonatal rat. Dev Brain Res 119(2):217–224

    Article  CAS  Google Scholar 

  • Zvarova K, Murray E, Vizzard MA (2004) Changes in galanin-immunoreactivity in rat lumbosacral spinal cord and dorsal root ganglia (DRG) after spinal cord injury (SCI). J Comp Neurol 475:590–603

    Article  PubMed  CAS  Google Scholar 

  • Zvarova K, Dunleavy JD, Vizzard MA (2005) Changes in pituitary adenylate cyclase activating polypeptide expression in urinary bladder pathways after spinal cord injury. Exp Neurol 192(1):46–59

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Margaret A. Vizzard.

Additional information

This work was supported in part through NIH grants DK051369, DK060481, DK065989, NS040796.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Studeny, S., Vizzard, M.A. Corticotropin-releasing factor (CRF) expression in postnatal and adult rat sacral parasympathetic nucleus (SPN). Cell Tissue Res 322, 339–352 (2005). https://doi.org/10.1007/s00441-005-0014-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-005-0014-2

Keywords

Navigation