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. 1968 Feb 1;36(2):379–390. doi: 10.1083/jcb.36.2.379

THE FINE STRUCTURE OF PUROMYCIN-INDUCED CHANGES IN MOUSE ENTORHINAL CORTEX

Pierluigi Gambetti 1, Nicholas K Gonatas 1, Louis B Flexner 1
PMCID: PMC2107358  PMID: 5638887

Abstract

Bitemporal intracerebral injections of puromycin in mice suppress indefinitely expression of memory of avoidance-discrimination learning. Ultrastructural studies of the entorhinal cortex of puromycin-treated mice revealed the following: (a) Abnormalities were not observed in presynaptic terminals and synaptic clefts; many postsynaptic dendrites or somas contained swollen mitochondria. (b) Dispersion of polyribosomes into single units or condensation of ribosomes into irregular aggregates with loss of "distinctiveness" was noted in a few neurons 7–27 hr after puromycin treatment. (c) Cytoplasmic aggregates of granular or amorphous material were frequently noted within otherwise normal neuronal perikarya. (d) Mitochondria in many neuronal perikarya and dendrites were swollen. Mitochondria in axons, presynaptic terminals, and glial cells were unaltered. The relationships between these lesions and the effect of puromycin on protein synthesis and memory are examined. It is suggested that the disaggregation of polysomes is too limited to explain the effect of puromycin on memory. Special emphasis is given to the swelling of mitochondria. The possible mechanisms and the significance of this lesion are discussed.

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Selected References

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  1. Barondes S. H., Cohen H. D. Puromycin effect on successive phases of memory storage. Science. 1966 Feb 4;151(3710):594–595. doi: 10.1126/science.151.3710.594. [DOI] [PubMed] [Google Scholar]
  2. Campbell M. K., Mahler H. R., Moore W. J., Tewari S. Protein synthesis systems from rat brain. Biochemistry. 1966 Apr;5(4):1174–1184. doi: 10.1021/bi00868a009. [DOI] [PubMed] [Google Scholar]
  3. Clark-Walker G. D., Linnane A. W. The biogenesis of mitochondria in Saccharomyces cerevisiae. A comparison between cytoplasmic respiratory-deficient mutant yeast and chlormaphenicol-inhibited wild type cells. J Cell Biol. 1967 Jul;34(1):1–14. doi: 10.1083/jcb.34.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Elul R. Dependence of synaptic transmission on protein metabolism of nerve cells: a possible electrokinetic mechanism of learning? Nature. 1966 Jun 11;210(5041):1127–1131. doi: 10.1038/2101127a0. [DOI] [PubMed] [Google Scholar]
  5. FLEXNER J. B., FLEXNER L. B., STELLAR E. Memory in mice as affected by intracerebral puromycin. Science. 1963 Jul 5;141(3575):57–59. doi: 10.1126/science.141.3575.57. [DOI] [PubMed] [Google Scholar]
  6. Flexner J. B., Flexner L. B. Restoration of expression of memory lost after treatment with puromycin. Proc Natl Acad Sci U S A. 1967 Jun;57(6):1651–1654. doi: 10.1073/pnas.57.6.1651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Flexner L. B., Flexner J. B. Effect of acetoxycycloheximide and of an acetoxycycloheximide-puromycin mixture on cerebral protein synthesis and memory in mice. Proc Natl Acad Sci U S A. 1966 Feb;55(2):369–374. doi: 10.1073/pnas.55.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Flexner L. B., Flexner J. B., Roberts R. B. Memory in mice analyzed with antibiotics. Antibiotics are useful to study stages of memory and to indicate molecular events which sustain memory. Science. 1967 Mar 17;155(3768):1377–1383. doi: 10.1126/science.155.3768.1377. [DOI] [PubMed] [Google Scholar]
  9. GORSKI J., AIZAWA Y., MUELLER G. C. Effect of puromycin in vivo on the synthesis of protein, RNA and phospholipids in rat tissues. Arch Biochem Biophys. 1961 Dec;95:508–511. doi: 10.1016/0003-9861(61)90183-7. [DOI] [PubMed] [Google Scholar]
  10. Gonatas N. K., Anderson W., Evangelista I. The contribution of altered synapses in the senile plaque: an electron microscopic study in Alzheimer's dementia. J Neuropathol Exp Neurol. 1967 Jan;26(1):25–39. doi: 10.1097/00005072-196701000-00003. [DOI] [PubMed] [Google Scholar]
  11. Gonatas N. K. Axonic and synaptic lesions in neuropsychiatric disorders. Nature. 1967 Apr 22;214(5086):352–355. doi: 10.1038/214352a0. [DOI] [PubMed] [Google Scholar]
  12. Gonatas N. K., Evangelista I., Walsh G. O. Axonic and synaptic changes in a case of psychomotor retardation: an electron microscopic study. J Neuropathol Exp Neurol. 1967 Apr;26(2):179–199. doi: 10.1097/00005072-196704000-00001. [DOI] [PubMed] [Google Scholar]
  13. Gonatas N. K., Goldehsohn E. S. Unusual neocortical presynaptic terminals in a patient with convulsions, mental retardation and cortical blindness: an electron microscopic study. J Neuropathol Exp Neurol. 1965 Oct;24(4):539–562. [PubMed] [Google Scholar]
  14. HUXLEY H. E., ZUBAY G. Preferential staining of nucleic acid-containing structures for electron microscopy. J Biophys Biochem Cytol. 1961 Nov;11:273–296. doi: 10.1083/jcb.11.2.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. KARLSSON U., SCHULTZ R. L. FIXATION OF THE CENTRAL NERVOUS SYSTEM FROM ELECTRON MICROSCOPY BY ALDEHYDE PERFUSION. I. PRESERVATION WITH ALDEHYDE PERFUSATES VERSUS DIRECT PERFUSION WITH OSMIUM TETROXIDE WITH SPECIAL REFERENCE TO MEMBRANES AND THE EXTRACELLULAR SPACE. J Ultrastruct Res. 1965 Feb;12:160–186. doi: 10.1016/s0022-5320(65)80014-4. [DOI] [PubMed] [Google Scholar]
  16. KOPAC M. J., MATEYKO G. M. Malignant nucleoli: cytological studies and perspectives. Ann N Y Acad Sci. 1958 Sep 5;73(1):237–282. doi: 10.1111/j.1749-6632.1959.tb40803.x. [DOI] [PubMed] [Google Scholar]
  17. KROON A. M. INHIBITORS OF MITOCHONDRIAL PROTEIN SYNTHESIS. Biochim Biophys Acta. 1963 Sep 17;76:165–166. [PubMed] [Google Scholar]
  18. LEHNINGER A. L. Water uptake and extrusion by mitochondria in relation to oxidative phosphorylation. Physiol Rev. 1962 Jul;42:467–517. doi: 10.1152/physrev.1962.42.3.467. [DOI] [PubMed] [Google Scholar]
  19. MILLONIG G. A modified procedure for lead staining of thin sections. J Biophys Biochem Cytol. 1961 Dec;11:736–739. doi: 10.1083/jcb.11.3.736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Masurovsky E. B., Bunge M. B., Bunge R. P. Cytological studies of organotypic cultures of rat dorsal root ganglia following X-irradiation in vitro. I. Changes in neurons and satellite cells. J Cell Biol. 1967 Feb;32(2):467–496. doi: 10.1083/jcb.32.2.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. NATHANS D. PUROMYCIN INHIBITION OF PROTEIN SYNTHESIS: INCORPORATION OF PUROMYCIN INTO PEPTIDE CHAINS. Proc Natl Acad Sci U S A. 1964 Apr;51:585–592. doi: 10.1073/pnas.51.4.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. PALAY S. L. Synapses in the central nervous system. J Biophys Biochem Cytol. 1956 Jul 25;2(4 Suppl):193–202. doi: 10.1083/jcb.2.4.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Roodyn D. B. Further study of factors affecting amino acid incorporation into protein by isolated mitochondria. Biochem J. 1965 Dec;97(3):782–793. doi: 10.1042/bj0970782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. SABATINI D. D., BENSCH K., BARRNETT R. J. Cytochemistry and electron microscopy. The preservation of cellular ultrastructure and enzymatic activity by aldehyde fixation. J Cell Biol. 1963 Apr;17:19–58. doi: 10.1083/jcb.17.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. SCHULTZ R. L., MAYNARD E. A., PEASE D. C. Electron microscopy of neurons and neuroglia of cerebral cortex and corpus callosum. Am J Anat. 1957 May;100(3):369–407. doi: 10.1002/aja.1001000305. [DOI] [PubMed] [Google Scholar]
  26. STUDZINSKI G. P. NUCLEOLUS-LIKE INCLUSIONS IN THE CYTOPLASM OF HELA CELLS TREATED WITH PUROMYCIN. Nature. 1964 Aug 22;203:883–884. doi: 10.1038/203883a0. [DOI] [PubMed] [Google Scholar]
  27. Shimizu N., Ishii S. Electron-microscopic observations on nucleolar extrusion in nerve cells of the rat hypothalamus. Z Zellforsch Mikrosk Anat. 1965 Jul 30;67(3):367–372. doi: 10.1007/BF00339382. [DOI] [PubMed] [Google Scholar]
  28. Sulkin D. F., Sulkin N. M. An electron microscopic study of autonomic ganglion cells of guinea pigs during ascorbic acid deficiency and partial inanition. Lab Invest. 1967 Jan;16(1):142–152. [PubMed] [Google Scholar]
  29. WILLIAMSON A. R., SCHWEET R. ROLE OF THE GENETIC MESSAGE IN POLYRIBOSOME FUNCTION. J Mol Biol. 1965 Feb;11:358–372. doi: 10.1016/s0022-2836(65)80063-8. [DOI] [PubMed] [Google Scholar]
  30. Wendell-Smith C. P., Blunt M. J., Baldwin F. The ultrastructural characterization of macroglial cell types. J Comp Neurol. 1966 Jun;127(2):219–240. doi: 10.1002/cne.901270207. [DOI] [PubMed] [Google Scholar]
  31. Yarmolinsky M. B., Haba G. L. INHIBITION BY PUROMYCIN OF AMINO ACID INCORPORATION INTO PROTEIN. Proc Natl Acad Sci U S A. 1959 Dec;45(12):1721–1729. doi: 10.1073/pnas.45.12.1721. [DOI] [PMC free article] [PubMed] [Google Scholar]

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