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Erschienen in: Brain Structure and Function 1/2004

01.11.2004 | Original Article

Loss of glia and neurons in the myenteric plexus of the aged Fischer 344 rat

verfasst von: Robert J. Phillips, Elizabeth J. Kieffer, Terry L. Powley

Erschienen in: Brain Structure and Function | Ausgabe 1/2004

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Abstract

Over the normal lifespan, a subpopulation of myenteric neurons in the small and large intestines dies. This loss is one possible mechanism for the disruptions of gastrointestinal function seen in the elderly. Little, however, is known about how the glia constituting the supportive cells of the myenteric plexus may change with aging and the losses of the enteric neurons. The goal of the present study, therefore, was to determine what, if any, changes occur in the glia associated with myenteric neurons in the aged gut. Two experimental groups, consisting of adult (5–6 months of age, n=8) or aged (26 months of age, n=8) virgin male Fischer 344 rats, fed ad libitum, were examined. The duodenum, jejunum, ileum, colon, and rectum from each rat were prepared as whole mounts, and indirect immunofluorescence was used to visualize the myenteric glia and neurons (antibodies to S-100 and the HuC/D protein, respectively). Separate counts of glia and neurons from the same specimens were determined, and these counts were expressed both as per ganglionic area and as per ganglion to correct for “dilution” effects resulting from age-associated changes in tissue area. Significant reductions in both the numbers of glia as well as neurons occurred in every region of the small and large intestine sampled from aged rats, except for the rectum, where a nonsignificant decrease was observed. Glial loss was proportional to neuronal death, suggesting an interdependency between the two cell types. Thus, an understanding of the nature of the neuron-glia interaction in the enteric nervous system may provide insight into the deterioration of function seen in the aged gut.
Literatur
Zurück zum Zitat Bishop AE, Carlei F, Lee V, Trojanowski J, Marangos PJ, Dahl D, Polak JM (1985) Combined immunostaining of neurofilaments, neuron specific enolase, GFAP and S-100. A possible means for assessing the morphological and functional status of the enteric nervous system. Histochemistry 82:93–97PubMed Bishop AE, Carlei F, Lee V, Trojanowski J, Marangos PJ, Dahl D, Polak JM (1985) Combined immunostaining of neurofilaments, neuron specific enolase, GFAP and S-100. A possible means for assessing the morphological and functional status of the enteric nervous system. Histochemistry 82:93–97PubMed
Zurück zum Zitat Brehmer A, Blaser B, Seitz G, Schrodl F, Neuhuber W (2004) Pattern of lipofuscin pigmentation in nitrergic and non-nitrergic, neurofilament immunoreactive myenteric neuron types of human small intestine. Histochem Cell Biol 121:13–20CrossRefPubMed Brehmer A, Blaser B, Seitz G, Schrodl F, Neuhuber W (2004) Pattern of lipofuscin pigmentation in nitrergic and non-nitrergic, neurofilament immunoreactive myenteric neuron types of human small intestine. Histochem Cell Biol 121:13–20CrossRefPubMed
Zurück zum Zitat Brookes SJ (2001) Classes of enteric nerve cells in the guinea-pig small intestine. Anat Rec 262:58–70CrossRefPubMed Brookes SJ (2001) Classes of enteric nerve cells in the guinea-pig small intestine. Anat Rec 262:58–70CrossRefPubMed
Zurück zum Zitat Bush TG, Savidge TC, Freeman TC, Cox HJ, Campbell EA, Mucke L, Johnson MH, Sofroniew MV (1998) Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice. Cell 93:189–201CrossRefPubMed Bush TG, Savidge TC, Freeman TC, Cox HJ, Campbell EA, Mucke L, Johnson MH, Sofroniew MV (1998) Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice. Cell 93:189–201CrossRefPubMed
Zurück zum Zitat Cabarrocas J, Savidge TC, Liblau RS (2003) Role of enteric glial cells in inflammatory bowel disease. Glia 41:81–93CrossRefPubMed Cabarrocas J, Savidge TC, Liblau RS (2003) Role of enteric glial cells in inflammatory bowel disease. Glia 41:81–93CrossRefPubMed
Zurück zum Zitat Corns RA, Hidaka H, Santer RM (2002) Neurocalcin-alpha immunoreactivity in the enteric nervous system of young and aged rats. Cell Calcium 31:53–58CrossRefPubMed Corns RA, Hidaka H, Santer RM (2002) Neurocalcin-alpha immunoreactivity in the enteric nervous system of young and aged rats. Cell Calcium 31:53–58CrossRefPubMed
Zurück zum Zitat Cowen T, Johnson RJ, Soubeyre V, Santer RM (2000) Restricted diet rescues rat enteric motor neurones from age related cell death. Gut 47:653–660CrossRefPubMed Cowen T, Johnson RJ, Soubeyre V, Santer RM (2000) Restricted diet rescues rat enteric motor neurones from age related cell death. Gut 47:653–660CrossRefPubMed
Zurück zum Zitat Ferrante F, Geppetti P, Amenta F (1991) Age-related changes in substance P and vasoactive intestinal polypeptide immunoreactivity in the rat stomach and small intestine. Arch Gerontol Geriatr 13:81–87CrossRefPubMed Ferrante F, Geppetti P, Amenta F (1991) Age-related changes in substance P and vasoactive intestinal polypeptide immunoreactivity in the rat stomach and small intestine. Arch Gerontol Geriatr 13:81–87CrossRefPubMed
Zurück zum Zitat Furness JB (2000) Types of neurons in the enteric nervous system. J Auton Nerv Syst 81:87–96CrossRefPubMed Furness JB (2000) Types of neurons in the enteric nervous system. J Auton Nerv Syst 81:87–96CrossRefPubMed
Zurück zum Zitat Gabella G (1971) Glia cells in the myenteric plexus. Zeitschrift Fur Naturforshung 26:244–245 Gabella G (1971) Glia cells in the myenteric plexus. Zeitschrift Fur Naturforshung 26:244–245
Zurück zum Zitat Gabella G (1984) Size of neurons and glial cells in the intramural ganglia of the hypertrophic intestine of the guinea-pig. J Neurocytol 13:73–84PubMed Gabella G (1984) Size of neurons and glial cells in the intramural ganglia of the hypertrophic intestine of the guinea-pig. J Neurocytol 13:73–84PubMed
Zurück zum Zitat Gabella G (1989) Fall in the number of myenteric neurons in aging guinea pigs. Gastroenterology 96:1487–1493PubMed Gabella G (1989) Fall in the number of myenteric neurons in aging guinea pigs. Gastroenterology 96:1487–1493PubMed
Zurück zum Zitat Gabella G, Trigg P (1984) Size of neurons and glial cells in the enteric ganglia of mice, guinea-pigs, rabbits and sheep. J Neurocytol 13:49–71PubMed Gabella G, Trigg P (1984) Size of neurons and glial cells in the enteric ganglia of mice, guinea-pigs, rabbits and sheep. J Neurocytol 13:49–71PubMed
Zurück zum Zitat Gershon MD (1998) V. Genes, lineages, and tissue interactions in the development of the enteric nervous system. Am J Physiol 275:G869–873PubMed Gershon MD (1998) V. Genes, lineages, and tissue interactions in the development of the enteric nervous system. Am J Physiol 275:G869–873PubMed
Zurück zum Zitat Hanani M, Reichenbach A (1994) Morphology of horseradish peroxidase (HRP)-injected glial cells in the myenteric plexus of the guinea-pig. Cell Tissue Res 278:153–160CrossRefPubMed Hanani M, Reichenbach A (1994) Morphology of horseradish peroxidase (HRP)-injected glial cells in the myenteric plexus of the guinea-pig. Cell Tissue Res 278:153–160CrossRefPubMed
Zurück zum Zitat Hanani M, Fellig Y, Udassin R, Freund HR (2004) Age-related changes in the morphology of the myenteric plexus of the human colon. Auton Neurosci 113:71–78CrossRefPubMed Hanani M, Fellig Y, Udassin R, Freund HR (2004) Age-related changes in the morphology of the myenteric plexus of the human colon. Auton Neurosci 113:71–78CrossRefPubMed
Zurück zum Zitat Hebel R, Stromberg MW (1976) Anatomy of the laboratory rat. Waverly Press, Baltimore Hebel R, Stromberg MW (1976) Anatomy of the laboratory rat. Waverly Press, Baltimore
Zurück zum Zitat Jessen KR, Mirsky R (1983) Astrocyte-like glia in the peripheral nervous system: an immunohistochemical study of enteric glia. J Neurosci 3:2206–2218PubMed Jessen KR, Mirsky R (1983) Astrocyte-like glia in the peripheral nervous system: an immunohistochemical study of enteric glia. J Neurosci 3:2206–2218PubMed
Zurück zum Zitat Johnson RJ, Schemann M, Santer RM, Cowen T (1998) The effects of age on the overall population and on sub-populations of myenteric neurons in the rat small intestine. J Anat 192:479–488CrossRefPubMed Johnson RJ, Schemann M, Santer RM, Cowen T (1998) The effects of age on the overall population and on sub-populations of myenteric neurons in the rat small intestine. J Anat 192:479–488CrossRefPubMed
Zurück zum Zitat Karaosmanoglu T, Aygun B, Wade PR, Gershon MD (1996) Regional differences in the number of neurons in the myenteric plexus of the guinea pig small intestine and colon: an evaluation of markers used to count neurons. Anat Rec 244:470–480CrossRefPubMed Karaosmanoglu T, Aygun B, Wade PR, Gershon MD (1996) Regional differences in the number of neurons in the myenteric plexus of the guinea pig small intestine and colon: an evaluation of markers used to count neurons. Anat Rec 244:470–480CrossRefPubMed
Zurück zum Zitat Kobayashi S, Suzuki M, Endo T, Tsuji S, Daniel EE (1986) Framework of the enteric nerve plexuses: an immunocytochemical study in the guinea pig jejunum using an antiserum to S-100 protein. Arch Histol Jpn 49:159–188PubMed Kobayashi S, Suzuki M, Endo T, Tsuji S, Daniel EE (1986) Framework of the enteric nerve plexuses: an immunocytochemical study in the guinea pig jejunum using an antiserum to S-100 protein. Arch Histol Jpn 49:159–188PubMed
Zurück zum Zitat Komuro T, Tokui K, Zhou DS (1996) Identification of the interstitial cells of Cajal. Histopathol 11:769–786PubMed Komuro T, Tokui K, Zhou DS (1996) Identification of the interstitial cells of Cajal. Histopathol 11:769–786PubMed
Zurück zum Zitat McDougal JN, Miller MS, Burks TF, Kreulen DL (1984) Age-related changes in colonic function in rats. Am J Physiol 247:G542–G546PubMed McDougal JN, Miller MS, Burks TF, Kreulen DL (1984) Age-related changes in colonic function in rats. Am J Physiol 247:G542–G546PubMed
Zurück zum Zitat Nada O, Kawana T (1988) Immunohistochemical identification of supportive cell types in the enteric nervous system of the rat colon and rectum. Cell Tissue Res 251:523–529CrossRefPubMed Nada O, Kawana T (1988) Immunohistochemical identification of supportive cell types in the enteric nervous system of the rat colon and rectum. Cell Tissue Res 251:523–529CrossRefPubMed
Zurück zum Zitat Lin Z, Gao N, Hu HZ, Liu S, Gao C, Kim G, Ren J, Xia Y, Peck OC, Wood JD (2002) Immunoreactivity of Hu proteins facilitates identification of myenteric neurones in guinea-pig small intestine. Neurogastroenterol Motil 14:197–204CrossRefPubMed Lin Z, Gao N, Hu HZ, Liu S, Gao C, Kim G, Ren J, Xia Y, Peck OC, Wood JD (2002) Immunoreactivity of Hu proteins facilitates identification of myenteric neurones in guinea-pig small intestine. Neurogastroenterol Motil 14:197–204CrossRefPubMed
Zurück zum Zitat Parr EJ, Sharkey KA (1997) Multiple mechanisms contribute to myenteric plexus ablation induced by benzalkonium chloride in the guinea-pig ileum. Cell Tissue Res 289:253–264CrossRefPubMed Parr EJ, Sharkey KA (1997) Multiple mechanisms contribute to myenteric plexus ablation induced by benzalkonium chloride in the guinea-pig ileum. Cell Tissue Res 289:253–264CrossRefPubMed
Zurück zum Zitat Patterson LM, Zheng H, Ward SM, Berthoud HR (2001) Immunohistochemical identification of cholecystokinin A receptors on interstitial cells of Cajal, smooth muscle, and enteric neurons in rat pylorus. Cell Tissue Res 305:11–23CrossRefPubMed Patterson LM, Zheng H, Ward SM, Berthoud HR (2001) Immunohistochemical identification of cholecystokinin A receptors on interstitial cells of Cajal, smooth muscle, and enteric neurons in rat pylorus. Cell Tissue Res 305:11–23CrossRefPubMed
Zurück zum Zitat Peters A (2002) Structural changes that occur during normal aging of primate cerebral hemispheres. Neurosci Biobehav Rev 26:733–741CrossRefPubMed Peters A (2002) Structural changes that occur during normal aging of primate cerebral hemispheres. Neurosci Biobehav Rev 26:733–741CrossRefPubMed
Zurück zum Zitat Phillips RJ, Powley TL (2001) As the gut ages: timetables for aging of innervation vary by organ in the Fischer 344 rat. J Comp Neurol 434:358–377CrossRefPubMed Phillips RJ, Powley TL (2001) As the gut ages: timetables for aging of innervation vary by organ in the Fischer 344 rat. J Comp Neurol 434:358–377CrossRefPubMed
Zurück zum Zitat Phillips RJ, Kieffer EJ, Powley TL (2003a) Aging of the myenteric plexus: neuronal loss is specific to cholinergic neurons. Auton Neurosci 106:69–83CrossRefPubMed Phillips RJ, Kieffer EJ, Powley TL (2003a) Aging of the myenteric plexus: neuronal loss is specific to cholinergic neurons. Auton Neurosci 106:69–83CrossRefPubMed
Zurück zum Zitat Phillips RJ, Kieffer EJ, Powley TL (2003b) Age-related losses of enteric glial cells are associated with neuronal death in the myenteric plexus of the small and large intestines. Program No. 393.10. Abstract viewer/itinerary planner. Society for Neuroscience, Washington, DC. Online Phillips RJ, Kieffer EJ, Powley TL (2003b) Age-related losses of enteric glial cells are associated with neuronal death in the myenteric plexus of the small and large intestines. Program No. 393.10. Abstract viewer/itinerary planner. Society for Neuroscience, Washington, DC. Online
Zurück zum Zitat Phillips RJ, Hargrave SL, Rhodes BS, Zopf DA, Powley TL (2004) Quantification of neurons in the myenteric plexus: an evaluation of putative pan-neuronal markers. J Neurosci Meth 133:99–107CrossRef Phillips RJ, Hargrave SL, Rhodes BS, Zopf DA, Powley TL (2004) Quantification of neurons in the myenteric plexus: an evaluation of putative pan-neuronal markers. J Neurosci Meth 133:99–107CrossRef
Zurück zum Zitat Ruhl A, Nasser Y, Sharkey KA (2004) Enteric Glia. Neurogastroenterol 16:44–49CrossRef Ruhl A, Nasser Y, Sharkey KA (2004) Enteric Glia. Neurogastroenterol 16:44–49CrossRef
Zurück zum Zitat Santer RM (1994) Survival of the population of NADPH-diaphorase stained myenteric neurons in the small intestine of aged rats. J Auton Nerv Syst 49:115–121CrossRefPubMed Santer RM (1994) Survival of the population of NADPH-diaphorase stained myenteric neurons in the small intestine of aged rats. J Auton Nerv Syst 49:115–121CrossRefPubMed
Zurück zum Zitat Santer RM, Baker DM (1988) Enteric neuron numbers and sizes in Auerbach’s plexus in the small and large intestine of adult and aged rats. J Auton Nerv Syst 25:59–67CrossRefPubMed Santer RM, Baker DM (1988) Enteric neuron numbers and sizes in Auerbach’s plexus in the small and large intestine of adult and aged rats. J Auton Nerv Syst 25:59–67CrossRefPubMed
Zurück zum Zitat Scheuermann DW, Stach W, Timmermans JP, Adriaensen D, De Groodt-Lasseel MH (1989) Neuron-specific enolase and S-100 protein immunohistochemistry for defining the structure and topographical relationship of the different enteric nerve plexuses in the small intestine of the pig. Cell Tissue Res 256:65–75CrossRefPubMed Scheuermann DW, Stach W, Timmermans JP, Adriaensen D, De Groodt-Lasseel MH (1989) Neuron-specific enolase and S-100 protein immunohistochemistry for defining the structure and topographical relationship of the different enteric nerve plexuses in the small intestine of the pig. Cell Tissue Res 256:65–75CrossRefPubMed
Zurück zum Zitat Smits GJM, Lefebvre RA (1996) Influence of aging on gastric emptying of liquids, small intestine transit, and fecal output in rats. Exp Gerontol 31:589–596CrossRefPubMed Smits GJM, Lefebvre RA (1996) Influence of aging on gastric emptying of liquids, small intestine transit, and fecal output in rats. Exp Gerontol 31:589–596CrossRefPubMed
Zurück zum Zitat Steinkamp M, Geerling I, Seufferlein T, von Boyen G, Egger B, Grossmann J, Ludwig L, Adler G, Reinshagen M (2003) Glial-derived neurotrophic factor regulates apoptosis in colonic epithelial cells. Gastroenterology 124:1748–1757CrossRefPubMed Steinkamp M, Geerling I, Seufferlein T, von Boyen G, Egger B, Grossmann J, Ludwig L, Adler G, Reinshagen M (2003) Glial-derived neurotrophic factor regulates apoptosis in colonic epithelial cells. Gastroenterology 124:1748–1757CrossRefPubMed
Zurück zum Zitat Turturro A, Witt WW, Lewis S, Hass BS, Lipman RD, Hart R (1999) Growth curves and survival characteristics of the animals used in the biomarkers of aging program. J Gerontol A Biol Sci Med Sci 54:B492–B501PubMed Turturro A, Witt WW, Lewis S, Hass BS, Lipman RD, Hart R (1999) Growth curves and survival characteristics of the animals used in the biomarkers of aging program. J Gerontol A Biol Sci Med Sci 54:B492–B501PubMed
Zurück zum Zitat Unger JW (1998) Glial reaction in aging and Alzheimer’s disease. Microsc Res Tech 43:24–28CrossRefPubMed Unger JW (1998) Glial reaction in aging and Alzheimer’s disease. Microsc Res Tech 43:24–28CrossRefPubMed
Zurück zum Zitat Varga F (1976) Transit time changes with age in the gastrointestinal tract of the rat. Digestion 14:319–324PubMed Varga F (1976) Transit time changes with age in the gastrointestinal tract of the rat. Digestion 14:319–324PubMed
Zurück zum Zitat Wade PR (2002) Aging and neural control of the GI tract. I. Age-related changes in the enteric nervous system. Am J Physiol Gastrointest Liver Physiol 283:G489–495PubMed Wade PR (2002) Aging and neural control of the GI tract. I. Age-related changes in the enteric nervous system. Am J Physiol Gastrointest Liver Physiol 283:G489–495PubMed
Zurück zum Zitat Wade PR, Cowen T (2004) Neurodegeneration: a key factor in the ageing gut. Neurogastroenterol Motil 16:19–23CrossRefPubMed Wade PR, Cowen T (2004) Neurodegeneration: a key factor in the ageing gut. Neurogastroenterol Motil 16:19–23CrossRefPubMed
Zurück zum Zitat Wedel T, Roblick UJ, Ott V, Eggers R, Schiedeck THK, Krammer H-J, Bruch H-P (2001) Oligoneuronal hypoganglionosis in patients with idiopathic slow-transit constipation. Dis Colon Rectum 45:54–62 Wedel T, Roblick UJ, Ott V, Eggers R, Schiedeck THK, Krammer H-J, Bruch H-P (2001) Oligoneuronal hypoganglionosis in patients with idiopathic slow-transit constipation. Dis Colon Rectum 45:54–62
Zurück zum Zitat Wu M, Van Nassauw L, Kroese AB, Adriaensen D, Timmermans JP (2003) Myenteric nitrergic neurons along the rat esophagus: evidence for regional and strain differences in age-related changes. Histochem Cell Biol 119:395–403PubMed Wu M, Van Nassauw L, Kroese AB, Adriaensen D, Timmermans JP (2003) Myenteric nitrergic neurons along the rat esophagus: evidence for regional and strain differences in age-related changes. Histochem Cell Biol 119:395–403PubMed
Metadaten
Titel
Loss of glia and neurons in the myenteric plexus of the aged Fischer 344 rat
verfasst von
Robert J. Phillips
Elizabeth J. Kieffer
Terry L. Powley
Publikationsdatum
01.11.2004
Verlag
Springer-Verlag
Erschienen in
Brain Structure and Function / Ausgabe 1/2004
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-004-0426-x

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