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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 Nov;88(5):1709–1715. doi: 10.1172/JCI115488

Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function.

W D Steers 1, S Kolbeck 1, D Creedon 1, J B Tuttle 1
PMCID: PMC295710  PMID: 1939656

Abstract

Urethral obstruction produces increased voiding frequency (0.7 +/- 0.06 to 1.1 +/- 0.08 h-1) and hypertrophy of the urinary bladder (89 +/- 1.7 to 708 +/- 40 mg) with profound increments in the dimensions of afferent (4, 6) and efferent neurons (299 +/- 4.7 to 573 +/- 8.6 microns2) supplying this organ in the rat. We discovered that hypertrophied bladders of rat and human contain significantly more nerve growth factor (NGF) per milligram wet weight, protein, and DNA than normal bladders. The temporal correlation between NGF content, neuronal hypertrophy, and bladder weight was consistent with a role for this growth factor in the neurotrophic effects associated with obstruction. Autoimmunity to NGF abolished the hypertrophy of NGF-sensitive bladder neurons in the pelvic ganglion after obstruction. Relief of urethral obstruction reduced bladder size (349 +/- 78 mg), but neuronal hypertrophy (460.2 +/- 10.2 microns2) and elevated NGF levels were only partially reversed. Bladder hypertrophy (133 +/- 4.3 mg) induced by osmotic diuresis slightly increased ganglion cell area (365.2 +/- 6.1 microns2) and only doubled NGF content of the bladder. These findings provide important new evidence that parenchymal cells in the hypertrophied bladder can synthesize NGF and possibly other molecular messengers that act to alter the size and function of neurons in adult animals and man.

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Selected References

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  1. Andersen J. T. Detrusor hyperreflexia in benign infravesical obstruction. a cystometic study. J Urol. 1976 May;115(5):532–534. doi: 10.1016/s0022-5347(17)59268-x. [DOI] [PubMed] [Google Scholar]
  2. Barde Y. A., Edgar D., Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1982;1(5):549–553. doi: 10.1002/j.1460-2075.1982.tb01207.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bjerre B., Rosengren E. Effects of nerve growth factor and its antiserum on axonal regeneration of short adrenergic neurons in the male mouse. Cell Tissue Res. 1974;150(3):299–322. doi: 10.1007/BF00220139. [DOI] [PubMed] [Google Scholar]
  4. Earlam R. J. Ganglion cell changes in experimental stenosis of the gut. Gut. 1971 May;12(5):393–398. doi: 10.1136/gut.12.5.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ebendal T., Olson L., Seiger A. The level of nerve growth factor (NGF) as a function of innervation. A correlation radio-immunoassay and bioassay study of the rat iris. Exp Cell Res. 1983 Oct 15;148(2):311–317. doi: 10.1016/0014-4827(83)90155-6. [DOI] [PubMed] [Google Scholar]
  6. Gabella G. Size of neurons and glial cells in the intramural ganglia of the hypertrophic intestine of the guinea-pig. J Neurocytol. 1984 Feb;13(1):73–84. doi: 10.1007/BF01148319. [DOI] [PubMed] [Google Scholar]
  7. Gorin P. D., Johnson E. M., Jr Effects of long-term nerve growth factor deprivation on the nervous system of the adult rat: an experimental autoimmune approach. Brain Res. 1980 Sep 29;198(1):27–42. doi: 10.1016/0006-8993(80)90341-8. [DOI] [PubMed] [Google Scholar]
  8. Hengerer B., Lindholm D., Heumann R., Rüther U., Wagner E. F., Thoenen H. Lesion-induced increase in nerve growth factor mRNA is mediated by c-fos. Proc Natl Acad Sci U S A. 1990 May;87(10):3899–3903. doi: 10.1073/pnas.87.10.3899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Holtgrewe H. L., Mebust W. K., Dowd J. B., Cockett A. T., Peters P. C., Proctor C. Transurethral prostatectomy: practice aspects of the dominant operation in American urology. J Urol. 1989 Feb;141(2):248–253. doi: 10.1016/s0022-5347(17)40732-4. [DOI] [PubMed] [Google Scholar]
  10. Keast J. R., de Groat W. C. Immunohistochemical characterization of pelvic neurons which project to the bladder, colon, or penis in rats. J Comp Neurol. 1989 Oct 15;288(3):387–400. doi: 10.1002/cne.902880303. [DOI] [PubMed] [Google Scholar]
  11. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  12. Marban E., Koretsune Y. Cell calcium, oncogenes, and hypertrophy. Hypertension. 1990 Jun;15(6 Pt 1):652–658. doi: 10.1161/01.hyp.15.6.652. [DOI] [PubMed] [Google Scholar]
  13. Meghji P., Tuttle J. B., Rubio R. Adenosine formation and release by embryonic chick neurons and glia in cell culture. J Neurochem. 1989 Dec;53(6):1852–1860. doi: 10.1111/j.1471-4159.1989.tb09252.x. [DOI] [PubMed] [Google Scholar]
  14. Purves D., Snider W. D., Voyvodic J. T. Trophic regulation of nerve cell morphology and innervation in the autonomic nervous system. Nature. 1988 Nov 10;336(6195):123–128. doi: 10.1038/336123a0. [DOI] [PubMed] [Google Scholar]
  15. Steers W. D., Ciambotti J., Erdman S., de Groat W. C. Morphological plasticity in efferent pathways to the urinary bladder of the rat following urethral obstruction. J Neurosci. 1990 Jun;10(6):1943–1951. doi: 10.1523/JNEUROSCI.10-06-01943.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Steers W. D., De Groat W. C. Effect of bladder outlet obstruction on micturition reflex pathways in the rat. J Urol. 1988 Oct;140(4):864–871. doi: 10.1016/s0022-5347(17)41846-5. [DOI] [PubMed] [Google Scholar]
  17. Uvelius B., Mattiasson A. Collagen content in the rat urinary bladder subjected to infravesical outflow obstruction. J Urol. 1984 Sep;132(3):587–590. doi: 10.1016/s0022-5347(17)49753-9. [DOI] [PubMed] [Google Scholar]
  18. Vaca K., Stewart S. S., Appel S. H. Identification of basic fibroblast growth factor as a cholinergic growth factor from human muscle. J Neurosci Res. 1989 May;23(1):55–63. doi: 10.1002/jnr.490230108. [DOI] [PubMed] [Google Scholar]
  19. Voyvodic J. T. Peripheral target regulation of dendritic geometry in the rat superior cervical ganglion. J Neurosci. 1989 Jun;9(6):1997–2010. doi: 10.1523/JNEUROSCI.09-06-01997.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Weskamp G., Otten U. An enzyme-linked immunoassay for nerve growth factor (NGF): a tool for studying regulatory mechanisms involved in NGF production in brain and in peripheral tissues. J Neurochem. 1987 Jun;48(6):1779–1786. doi: 10.1111/j.1471-4159.1987.tb05736.x. [DOI] [PubMed] [Google Scholar]

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