Skip to main content
Top
Published 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

Authors: Robert J. Phillips, Elizabeth J. Kieffer, Terry L. Powley

Published in: Brain Structure and Function | Issue 1/2004

Login to get access

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.
Literature
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
go back to reference 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
Metadata
Title
Loss of glia and neurons in the myenteric plexus of the aged Fischer 344 rat
Authors
Robert J. Phillips
Elizabeth J. Kieffer
Terry L. Powley
Publication date
01-11-2004
Publisher
Springer-Verlag
Published in
Brain Structure and Function / Issue 1/2004
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-004-0426-x

Other articles of this Issue 1/2004

Brain Structure and Function 1/2004 Go to the issue