[en] The 27-kDa heat shock protein (Hsp27) is constitutively expressed in motor and sensory neurons of the brainstem. Hsp27 is also rapidly induced in the nervous system following oxidative and cellular metabolic stress. In this study, we examined the distribution of Hsp27 in the rat medulla oblongata by means of immunohistochemistry after the vagus nerve was cut or crushed. After vagal injury, rats were allowed to survive for 6, 12, 24 h, 2, 4, 7, 10, 14, 30, or 90 days. Vagus nerve lesions resulted in a time-dependent up-regulation of Hsp27 in vagal motor and nodose ganglion sensory neurons that expressed Hsp27 constitutively and de novo induction in neurons that did not express Hsp27 constitutively. In the dorsal motor nucleus of the vagus nerve (DMV) and nucleus ambiguus, the levels of Hsp27 in motor neurons were elevated within 24 h of injury and persisted for up to 90 days. Vagal afferents to the nucleus of the tractus solitarius (NTS) and area postrema showed increases in Hsp27 levels within 4 days that were still present 90 days postinjury. In addition, increases in Hsp27 staining of axons in the NTS and DMV suggest that vagus nerve injury resulted in sprouting of afferent axons and spread into areas of the dorsal vagal complex not normally innervated by the vagus. Our observations are consistent with the possibility that Hsp27 plays a role in long-term survival of distinct subpopulations of injured vagal motor and sensory neurons.
Aldskogius H., Barron K. D., Regal R. Axon reaction in dorsal motor vagal and hypoglossal neurons of the adult rat. Light microscopy and RNA-cytochemistry. J. Comp. Neurol. 193:1980;165-177.
Altschuler S. M., Bao X., Bieger D., Hopkins D. A., Miselis R. R. Viscerotopic representation of the upper alimentary tract in the rat: Sensory ganglia and nuclei of the solitary and spinal trigeminal tracts. J. Comp. Neurol. 283:1989;248-268.
Arrigo A.-P., Landry J. Expression and function of the low-molecular-weight heat shock proteins. The Biology of Heat Shock Proteins and Molecular Chaperones. 1994;Cold Spring Harbor Laboratory Press, New York. p. 335-373.
Bieger D., Hopkins D. A. Viscerotopic representation of the upper alimentary tract in the medulla oblongata in the rat: The nucleus ambiguus. J. Comp. Neurol. 262:1987;546-562.
Cameron A. A., Cliffer K. D., Dougherty P. M., Garrison C. J., Willis W. D., Carlton S. M. Time course of degenerative and regenerative changes in the dorsal horn in a rat model of peripheral neuropathy. J. Comp. Neurol. 379:1997;428-442.
Chrétien P., Landry J. Enhanced constitutive expression of the 27-kDa heat shock proteins in heat-resistant variants from Chinese hamster cells. J. Cell Physiol. 137:1988;157-166.
Clark B. D., Brown I. R. Axonal transport of a heat shock protein in the rabbit visual system. Proc. Nat. Acad. Sci. USA. 82:1985;1281-1285.
Fox E. A., Powley T. L. Morphology of identified preganglionic neurons in the dorsal motor nucleus of the vagus. J. Comp. Neurol. 322:1992;79-98.
Gernold M., Knauf U., Gaestel M., Stahl J., Kloetzel P.-M. Development and tissue-specific distribution of mouse small heat shock protein hsp25. Dev. Genet. 14:1993;103-111.
Gonzalez M. F., Sharp F. R., Sagar S. M. Axotomy increases NADPH-diaphorase staining in rat vagal motor neurons. Brain Res. Bull. 18:1987;417-427.
Herdegen T., Brecht S., Mayer B., Leah J., Kummer W., Bravo R., Zimmermann M. Long-lasting expression of JUN and KROX transcription factors and nitric oxide synthase in intrinsic neurons of the rat brain following axotomy. J. Neurosci. 13:1993;4130-4145.
Herdegen T., Kummer W., Fiallos C. E., Leah J., Bravo R. Expression of c-JUN, JUN B and JUN D proteins in rat nervous system following transection of vagus nerve and cervical sympathetic trunk. Neuroscience. 45:1991;413-422.
Hoover D. B., Hancock J. C., DePorter T. E. Effect of vagotomy on cholinergic parameters in nuclei of rat medulla oblongata. Brain Res. Bull. 15:1985;5-11.
Hopkins D. A., Bieger D., de Vente J., Steinbusch H. W. M. Vagal efferent projections: Viscerotopy, neurochemistry and effects of vagotomy. Prog. Brain Res. 107:1996;79-96.
Hopkins D. A., Ellenberger H. H. Cardiorespiratory neurons in the medulla oblongata: Input and output relationships. Armour J. A., Ardell J. L. Neurocardiology. 1994;277-307 Oxford University Press, New York.
Hopkins D. A., Plumier J.-C. L., Currie R. W. Induction of the 27-kDa heat shock protein (Hsp27) and nitric oxide synthase (NOS) in the rat medulla oblongata after vagotomy. Soc. Neurosci. Abstr. 23:1997;2371.
Houenou L. J., Li L., Lei M., Kent C. R., Tytell M. Exogenous heat shock cognate protein Hsc70 prevents axotomy-induced death of spinal sensory neurons. Cell Stress Chaperones. 1:1996;161-166.
Jakob U., Buchner J. Assisting spontaneity: The role of Hsp90 and small Hsps as molecular chaperones. Trends Biochem. Sci. 19:1994;205-211.
Jakob U., Gaestel M., Engel K., Buchner J. Small heat shock proteins are molecular chaperones. J. Biol. Chem. 268:1993;1517-1520.
Klemenz R., Andres A.-C., Fröhli E., Schäfer R., Ayoama A. Expression of the murine small heat shock proteins Hsp25 and αB-crystallin in the absence of stress. J. Cell Biol. 120:1993;639-645.
Kou S. Y., Chiu A. Y., Patterson P. H. Differential regulation of motor neuron survival and choline acetyltransferase expression following axotomy. J. Neurobiol. 27:1995;561-572.
Kristensson K., Aldskogius M., Peng Z.-C., Olsson T., Aldskogius H., Bentivoglio M. Co-induction of neuronal interferon-gamma and nitric oxide synthase in rat motor neurons after axotomy: A role in nerve repair or death. J. Neurocytol. 23:1994;453-459.
Krueger A. M., Armstrong J. N., Hopkins D. A., Robertson H. A., Currie R. W. The 27-kDa heat shock protein (Hsp27) is elevated in the cerebellum and brainstem of the rat following hyperthermia. Soc. Neurosci. Abstr. 23:1997;2264.
Lams B. E., Isacson O., Sofroniew M. V. Loss of transmitter-associated enzyme staining following axotomy does not indicate death of brainstem cholinergic neurons. Brain Res. 475:1988;401-406.
Landry J., Chrétien P., Lambert H., Hickey E., Weber L. A. Heat shock resistance conferred by expression of the human HSP27 gene in rodent cells. J. Cell Biol. 109:1989;7-15.
Lavoie J. N., Gingras-Breton G., Tanguay R. M., Landry J. Induction of Chinese hamster HSP27 gene expression in mouse cells confers resistance to heat shock. HSP27 stabilization of the microfilament organization. J. Biol. Chem. 268:1993;3420-3429.
Leslie R. A., Gwyn D. G., Hopkins D. A. The central distribution of the cervical vagus nerve and gastric afferent and efferent projections in the rat. Brain Res. Bull. 8:1982;37-43.
Lewis P. R., Blundell Jones P., Breathnach S. M., Navaratnam V. Regeneration capacity of visceral preganglionic neurones. Nature New Biol. 236:1972;181-182.
Lindquist S. The heat-shock response. Annu. Rev. Biochem. 55:1986;1151-1191.
Mannion R. J., Doubell T. P., Coggeshall R. E., Woolf C. J. Collateral sprouting of uninjured primary afferent A-fibers into the superficial dorsal horn of the adult rat spinal cord after topical capsaicin treatment to the sciatic nerve. J. Neurosci. 15:1996;5189-5195.
McMahon S. B., Kett-White R. Sprouting of peripherally regenerating primary sensory neurones in the adult central nervous system. J. Comp. Neurol. 304:1991;307-315.
Mehlen P., Kretz-Remy C., Préville X., Arrigo A.-P. Human Hsp27, Drosophila Hsp27 and human αB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFα-induced cell death. EMBO J. 15:1996;2695-2706.
Mehlen P., Préville X., Chareyron P., Briolay J., Klementz R., Arrigo A.-P. Constitutive expression of human Hsp27, Drosophila Hsp27, or human alpha B-crystallin confer resistance to TNF- and oxidative stress-induced cytotoxicity in stably transfected murine L929 fibroblasts. J. Immunol. 154:1995;363-374.
Mehlen P., Schulze-Osthoff K., Arrigo A.-P. Small stress proteins as novel regulators of apoptosis. Heat shock protein 27 blocks FAS/APO-1 and staurosporine-induced cell death. J. Biol. Chem. 271:1996;16510-16514.
Mesulam M.-M. Tetramethyl benzidine for horseradish peroxidase neurohistochemistry: A noncarcinogenic blue reaction product with superior sensitivity for visualizing neural afferents and efferents. J. Histochem. Cytochem. 26:1978;106-117.
Miron T., Vancompernolle K., Vandekerckhove J., Wilchek M., Geiger B. A 25-kD inhibitor of actin polymerization is a low molecular mass heat-shock protein. J. Cell Biol. 114:1991;255-261.
Miron T., Wilchek M., Geiger B. Characterization of an inhibitor of actin polymerization in vinculin-rich fraction of turkey gizzard smooth muscle. Eur. J. Biochem. 178:1988;543-553.
New G. A., Hendrickson B. R., Jones K. J. Induction of heat shock protein 70 mRNA in adult hamster facial nuclear groups following axotomy of the facial nerve. Metab. Brain Dis. 4:1989;273-279.
Plumier J.-C. L., Armstrong J. N., Landry J., Babity J. M., Robertson H. A., Currie R. W. Expression of the 27,000 mol wt heat shock protein following kainic acid-induced status epilepticus in the rat. Neuroscience. 75:1996;849-856.
Plumier J.-C. L., Armstrong J. N., Wood N. I., Babity J. M., Hamilton T. C., Hunter A. J., Robertson H. A., Currie R. W. Differential expression of c-fos, Hsp70 and Hsp27 after photothrombotic injury in the rat brain. Mol. Brain Res. 45:1997;239-246.
Plumier J.-C. L., Currie R. W. Heat shock-induced myocardial protection against ischemic injury: A role for Hsp70. Cell Stress Chaperones. 1:1996;13-17.
Plumier J.-C. L., David J.-C., Robertson H. A., Currie R. W. Cortical application of potassium chloride induces the low molecular weight heat shock protein (Hsp27) in astrocytes. J. Cereb. Blood Flow Metab. 17:1997;781-790.
Plumier J.-C. L., Hopkins D. A., Robertson H. A., Currie R. W. Constitutive expression of the 27-kDa heat shock Protein (Hsp27) in sensory and motor neurons of the rat nervous system. J. Comp. Neurol. 384:1997;409-428.
Plumier J.-C. L., Krueger A. M., Currie R. W., Kontoyiannis D., Kollias G., Pagoulatos G. N. Response of transgenic mice expressing the human 70-kDa heat shock protein to cerebral ischemia. Cell Stress Chaperones. 2:1997;162-167.
Plumier J.-C. L., Ross B. M., Currie R. W., Angelidis C. E., Kazlaris H., Kollias G., Pagoulatos G. N. Transgenic mice expressing the human HSP70 have improved post-ischemic myocardial recovery. J. Clin. Invest. 95:1995;1854-1860.
Rinaman L., Card J. P., Schwaber J. S., Miselis R. R. Ultrastructural demonstration of a gastric monosynaptic vagal circuit in the nucleus of the solitary tract in rat. J. Neurosci. 9:1989;1985-1996.
Ruggiero D. A., Mtui E. P., Otake K., Anwar M. Central and primary visceral afferents to nucleus tractus solitarii may generate nitric oxide as a membrane-permeant neuronal messenger. J. Comp. Neurol. 364:1996;51-67.
Rutherfurd S. D., Widdop R. E., Louis W. J., Gundlach A. L. Preprogalanin mRNA is increased in vagal motor neurons following axotomy. Mol. Brain Res. 14:1992;261-266.
Shapiro R. E., Miselis R. R. The central organization of the vagus nerve innervating the stomach of the rat. J. Comp. Neurol. 238:1985;473-488.
Tanguay R. M., Wu Y., Khandjian E. W. Tissue-specific expression of heat shock proteins of the mouse in the absence of stress. Dev. Genet. 14:1993;112-118.
Tedeschi B., Ciavarra R. P. Differential effects of axotomy on thein vivo. Mol. Brain Res. 45:1997;199-206.
Walsh D., Li Z., Wu Y., Nagata K. Heat shock and the role of the HSPs during neural plate induction in early mammalian CNS and brain development. Cell. Mol. Life Sci. 53:1997;198-211.
Welch W. J. The mammalian stress response: Cell physiology and biochemistry of stress proteins. Morimoto R. I., Tissières A., Georgopoulos C. Stress Proteins in Biology and Medicine. 1990;223-278 Cold Spring Harbor Laboratory Press, New York.
Welch W. J. Mammalian stress response: Cell physiology, structure/function of stress proteins, and implications for medicine and disease. Physiol. Rev. 72:1992;1063-1081.
