Preferences help
enabled [disable] Abstract
Number of results
2000 | 47 | 2 | 313-330
Article title

Does senile impairment of cholinergic system in rats concern only disturbances in cholinergic phenotype or the progressive degeneration of neuronal cell bodies?

Title variants
Languages of publication
The trophic effect of continuous intraventricular infusion of nerve growth factor (NGF) on morphology of the basal forebrain (BF) cholinergic neurons was tested in 4- and 28-month-old male Wistar rats. All studies were conducted using behaviorally uncharacterized animals from the same breeding colony. Immunohistochemical procedure for choline acetyltransferase (ChAT) and p75NTR receptor has been applied to identify cholinergic cells in the structures of basal forebrain (BF). Using a quantitative image analyzer, morphometric and densitometric parameters of ChAT- and p75NTR-positive cells were measured immediately after cessation of NGF infusion. In 28-month-old non-treated rats the number of intensively ChAT-positive cells in all forebrain structures was reduced by 50-70% as compared with young animals. The remaining ChAT-positive cells appeared shrunken and the neuropil staining was markedly reduced. In contrast, the same neurons when stained for p75NTR were numerous and distinctly visible with perfect morphology. Analysis of Nissl stained sections also showed that 28-month-old rats did not display significant losses of neuronal cell bodies. NGF restored the number of intensely stained ChAT-positive cells to about 90% of that for young controls and caused a significant increase in size of those cells in 28-month-old rats as compared with the control, age-matched group. NGF did not influence the morphology of p75NTR-positive neurons, which were well labeled, irrespective of treatment and age of the rats. In 4-month-old rats, NGF infusion decreased the intensity of both ChAT and p75NTR immunostaining. These data provide some evidence for preservation of BF cholinergic neurons from atrophy during aging and indicate that senile impairment of the cholinergic system in rats concerns decrease in ChAT-protein expression rather than an acute degeneration of neuronal cell bodies. Treatment with NGF resulted in restoration of cholinergic phenotype in the BF neurons of aged rats. However, the present study also rises issue of possible detrimental effects of NGF in young normal animals.
Physical description
  • Department of Neurophysiology, Nencki Institute, Warszawa, Poland
  • Department of Neurophysiology, Nencki Institute, Warszawa, Poland
  • Department of Neurophysiology, Nencki Institute, Warszawa, Poland
  • Beers, R.F. & Sizer, J.W. (1952) A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J. Biol. Chem. 195, 133-138.
  • Biliński, T., Krawiec, Z., Liczmański, A. & Litwińska, J. (1985) Is hydroxyl radical generated by the Fenton reaction in vivo? Biochem. Biophys. Res. Commun. 130, 533-539.
  • Biliński, T., Łukaszkiewicz, J. & Śledziewski, A. (1978) Demonstration of anaerobic catalase synthesis in the cz1 mutant of Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 83, 1225-1233.
  • Costa, V., Reis, E., Quintanilha, A. & Moradas- Fereira, P. (1993) Acquisition of ethanol tolerance in Saccharomyces cerevisiae. Key role of mitochondrial superoxide dismutase. Arch. Biochem. Biophys. 300, 608-614.
  • Davidson, J.F., Whyte, B., Bissinger, P.H. & Schiestl, R.H. (1996) Oxidative stress is involved in heat-induced cell death in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 93, 5116-5121.
  • Flattery-O'Brien, J.A., Grant, C.M. & Dawes, I.W. (1997) Stationary-phase regulation of the Saccharomyces cerevisiae SOD2 gene is dependent on additive effects of HAP2/3/4/5- and STRE-binding elements. Mol. Microbiol. 23, 303-312.
  • Gems, D. (1999) Nematode ageing: Putting metabolic theories to the test. Curr. Biol. 9, R614-R616.
  • Jaruga, E., Lapshina, E.A., Bilinski, T., Plonka, A. & Bartosz, G. (1995) Resistance to ionizing radiation and antioxidative defence in yeasts. Are antioxidant-deficient cells permanently stressed? Biochem. Mol. Biol. Int. 37, 467-473.
  • Jazwinski, S.M. (1990) Aging and senescence of the budding yeast Saccharomyces cerevisiae. Mol. Microbiol. 4, 337-343.
  • Jazwinski, S.M. (1996) Longevity, genes, and aging. Science 273, 54-59.
  • Kapahi, P., Boulton, M.E. & Kirkwood, T.B. (1999) Positive correlation between mammalian life span and cellular resistance to stress. Free Radic Biol. Med. 26, 495-500.
  • Kennedy, B.K., Austriaco, N.R.J., Zhang, J. & Guarente, L. (1995) Mutation in the silencing gene SIR4 can delay aging in S. cerevisiae. Cell 80, 485-496.
  • Kim, S., Kirchman, P.A., Benguria, A. & Jazwinski, S.M. (1999) in Methods in Aging Research (Yu, B.P., ed.) 2nd edn., pp. 191-213, CRC Press, Boca Raton, Boston, London, New York, Washington.
  • Lee, J., Dawes, I.W. & Roe, J.H. (1995) Adaptive response of Schizosaccharomyces pombe to hydrogen peroxide and menadione. Microbiology 141, 3127-3132.
  • Lee, S.M. & Park, J.W. (1998) Thermosensitive phenotype of yeast mutant lacking thioredoxin peroxidase. Arch. Biochem. Biophys. 359, 99-106.
  • Martinez-Pastor, M., Marchler, G., Schuller, C., Marchler, B.A., Ruis, H. & Estruch, F. (1996) The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE). EMBO J. 15, 2227-2235.
  • Meaden, P.G., Arneborg, N., Guldfeldt, L.U., Siegumfeldt, H. & Jakobsen, M. (1999) Endocytosis and vacuolar morphology in Saccharomyces cerevisiae are altered in response to ethanol stress or heat shock. Yeast 15, 1211- 1222.
  • Orr, W.C. & Sohal, R.S. (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263, 1128-1130.
  • Seymour, I.J. & Piper, P.W. (1999) Stress induction of HSP30, the plasma membrane heat shock protein gene of Saccharomyces cerevisiae, appears not to use known stress-regulated transcription factors. Microbiology 145, 231-239.
  • Shama, S., Kirchman, P.A., Jiang, J.C. & Jazwinski, S.M. (1998a) Role of RAS2 in recovery from chronic stress: Effect on yeast life span. Exp. Cell Res. 245, 368-378.
  • Shama, S., Lai, C.-Y., Antoniazzi, J.M., Jiang, J.C. & Jazwinski, S.M. (1998b) Heat stress-induced life span extension in yeast. Exp. Cell Res. 245, 379-388.
  • VanLoon, A.P.G.M., Persold-Hurt, B. & Schatz, G.A. (1986) A yeast mutant lacking mitochondrial manganese superoxide dismutase. Proc. Natl. Acad. Sci. U.S.A. 83, 3820-3824.
  • Wawryn, J., Krzepilko, A., Myszka, A. & Biliński, T. (1999) Deficiency in superoxide dismutases shortens life span of yeast cells. Acta Biochim. Polon. 46, 249-253.
  • Wieser, R., Adam, G., Wagner, A., Schüller, Ch., Marchler, G., Ruis, H., Krawiec, Z. & Bilinski, T. (1991) Heat shock factor-independent heat control of transcription of the CTT1 gene encoding the cytosolic catalase T of Saccharomyces cerevisiae. J. Biol. Chem. 266, 12406- 12411.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.