Neurochemical Research

, Volume 11, Issue 10, pp 1383–1395 | Cite as

Effects of pre-weaning undernutrition and post-weaning rehabilitation on polyphosphoinositide pools in rat brain regions

  • Uma S. Ananth
  • C. V. Ramakrishnan
  • George Hauser
Original Articles


In order to assess the effects of undernutrition during the pre-weaning period on polyphosphoinositide (PolyPI) pools in rat cerebral cortex, brain stem, and cerebellum, dams were fed 5% (L) or 22% (L+) protein diets from birth to weaning and the pups were used at this age for analyses. To examine rehabilitation post-weaning, L and L+ pups were fed 22% protein diets (P+) for an additional six week period. Rats were decapitated and the dissection begun either immediately (“0 min” samples) or 10 min later (10 min samples). Body and tissue weights, and cerebroside levels were determined in addition to PolyPI concentrations. In brain the extent of disappearance of PolyPI during the 10 min post-mortem period paralleled the content of gray matter: cerebral cortex > cerebellum > brain stem in all groups regardless of diet. Levels of PtdIns4P and PtdIns4,5P2 were decreased by 40% and 70% respectively in cerebral cortex of L “0 min” samples. Deficits of both lipids in brain stem and cerebellum were 40–50%. In the L 10 min samples, deficits were 20–30% in all three regions as compared with L+ 10 min levels, indicating the presence of a portion of both lipids affected only moderately by nutritional insufficiency. The effects on this relatively inert pool, much of it localized in myelin, were reversed on nutritional rehabilitation. The Poly PI pool lost post-mortem in L+ brain regions was practically absent in L brain regions and was not restored in L P+ animals. Thus, this study indicates that a metabolically labile pool, primarily located in gray matter structures, is more sensitive to nutritional deprivation during the pre-weaning period than the more stable pool. The precise role and function of these pools remain to be determined.


Brain Region Cerebral Cortex Gray Matter Brain Stem Protein Diet 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Eichberg, J. andDawson, R. M. C. 1965. Polyphosphoinositides in myelin. Biochem. J. 96:644–650.PubMedGoogle Scholar
  2. 2.
    Eichberg, J., Hauser, G., andShein, H. M. 1971. Polyphosphoinositides in normal and neoplastic rodent astrocytes. Biochem. Biophys. Res. Commun. 45:43–50.PubMedGoogle Scholar
  3. 3.
    Hauser, G., Eichberg, J., andGonzalez-Sastre F. 1971. Regional distribution of polyphosphoinositides in rat brain. Biochim. Biophys. Acta 248:87–95.PubMedGoogle Scholar
  4. 4.
    Gonzalez-Sastre, F., Eichberg, J., andHauser, G. 1971. Metabolic pools of polyphosphoinositides in rat brain. Biochim. Biophys. Acta 248:96–104.PubMedGoogle Scholar
  5. 5.
    Eichberg, J., andHauser, G. 1973. The subcellular distribution of polyphosphoinositides in myelinated and unmyelinated rat brain. Biochim. Biophys. Acta 326:210–223.PubMedGoogle Scholar
  6. 6.
    Deshmukh, D. S., Kuizon, S., Bear, W. D., andBrockerhoff, H. 1980. Distribution of phosphoinositides among subfractions of rat brain myelin. Lipids 15:14–18.PubMedGoogle Scholar
  7. 7.
    Uma, S., andRamakrishnan, C. V. 1983. Studies on polyphosphoinositides in developing rat brain. J. Neurochem. 40:914–916.PubMedGoogle Scholar
  8. 8.
    Deshmukh, D. S., Bear, W. D., andBrockerhoff, H. 1978. Polyphosphoinositide biosynthesis in three subfractions of rat brain myelin. J. Neurochem. 30:1191–1193.PubMedGoogle Scholar
  9. 9.
    Deshmukh, D. S., Kuizon, S., Bear, W. D., andBrockerhoff, H. 1982. Polyphosphoinositide mono- and diphosphoesterases of three subfractions of rat brain myelin. Neurochem. Res. 7:617–626.PubMedGoogle Scholar
  10. 10.
    Sheltawy, A., andDawson, R. M. C. 1969. The deposition and metabolism of polyphosphoinositides in rat and guinea-pig brain during development. Biochem. J. 111:147–155.PubMedGoogle Scholar
  11. 11.
    Birnberger, A. C., andEliasson, S. G. 1970. Experimental ischemia and polyphosphoinositide metabolism. Neurology 20:356–360.PubMedGoogle Scholar
  12. 12.
    Downes, P., andMichell, R. H. 1982. Phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate: Lipids in search of a function. Cell Calcium 3:467–502.PubMedGoogle Scholar
  13. 13.
    Abdel-Latif, A. A. 1983. Metabolism of phosphoinositides. Pages 91–131,in Lajtha A. (ed.), Handbook of Neurochemistry, Vol. 3, second edition, Plenum Press, New York.Google Scholar
  14. 14.
    Berridge, M. J. 1984. Inositol trisphosphate and diacylglycerol as second messengers. Biochem. J. 220:345–360.PubMedGoogle Scholar
  15. 15.
    Hokin, L. E. 1985. Receptors and phosphoinositide-generated second messengers. Ann. Rev. Biochem. 54:204–235.Google Scholar
  16. 16.
    Hirasawa, K. andNishizuka, Y. 1985. Phosphatidyl inositol turnover in receptor mechanism and signal transduction. Ann. Rev. Pharmacol. Toxicol. 25:147–170.Google Scholar
  17. 17.
    Dickerson, J. W. T., andJarvis, J. 1970. The effects of undernutrition and rehabilitation on the growth and chemical composition of the cerebellum, brain stem and forebrain of the rat. Proc. Nutr. Soc. 27:4A-5A.Google Scholar
  18. 18.
    Rajakakshmi andNakhasi, H. L. 1974. Effects of post-weaning protein deficiency on lipid composition in different regions of the brain in rats. Ind. J. Biochem. Biophys. 11:307–308.Google Scholar
  19. 19.
    Reddy, P. V. andSastry, P. S. 1979. Studies on neurotransmitter stimulated phospholipid metabolism with cerebral tissue suspensions and possible biochemical correlates of synaptogenesis in normal and undernourished rats. Brain Res. 168:287–298.PubMedGoogle Scholar
  20. 20.
    Reddy, T. S., Rajalakshmi, R. andRamakrishnan, C. V. 1982. Effects of nutritional rehabilitation on the content and lipid composition of brain gray and white matter of neonatally undernourished rats. J. Neurochem. 39:1297–1301.PubMedGoogle Scholar
  21. 21.
    Uma, S., andRamakrishnan, C. V. 1983. Effects of preweaning undernutrition and continued postweaning undernutrition or nutritional rehabilitation of polyphosphoinositides in rat brain. J. Neurochem. 40:1026–1029.PubMedGoogle Scholar
  22. 22.
    Hauser, G., andSwaminathan, U. 1982. Polyphosphoinositide pools in brain areas of protein-deprived weanling rats. Trans. Am. Soc. Neurochem. 13:150.Google Scholar
  23. 23.
    Hauser, G., andAnanth, U. 1983. Polyphosphoinositide pools in brain areas of undernourished and rehabilitated rats. J. Neurochem. 41 (Suppl):S-133.Google Scholar
  24. 24.
    Pappu, A., andHauser, G. 1981. Alterations of phospholipid metabolism in rat cerebral cortex mince induced by cationic amphiphilic drugs. J. Neurochem. 37:1006–1014.PubMedGoogle Scholar
  25. 25.
    Rouser, G., Siakotos, A. W., andFleischer, S. 1966. Quantitative analysis of phospholipids by thin-layer chromatography and phosphorus analysis of spots. Lipids 1:85–86.Google Scholar
  26. 26.
    Jungalwala, F. B., Hayes, L., andMcCluer, R. H. 1977. Determination of less than a nanomole of cerebrosides by high performance liquid chromatography with gradient elution analysis. J. Lipid Res. 18:285–292.PubMedGoogle Scholar
  27. 27.
    Lewin, E., andHess, H. H. 1965. Intralaminar distribution of cerebrosides in human frontal cortex. J. Neurochem. 12:213–220.PubMedGoogle Scholar
  28. 28.
    Norton, W. T. 1981. Formation, structure and biochemistry of myelin. Pages 63–92,in Siegel, G. J., Albers, R. W., Agranoff, B. W., andKatzman, R. (eds.) Basic Neurochemistry, third edition, Little, Brown and Company, Boston.Google Scholar
  29. 29.
    Muller, A. J., andCox, W. M. 1946. The effect of changes in diet on the volume and composition of rat milk. J. Nutr. 31:249–259.Google Scholar
  30. 30.
    Venkatachalam, P., andRamanathan, K. S. 1964. Effect of protein deficiency during gestation and lactation on body weight and composition of offspring. J. Nutr. 103:213–217.Google Scholar
  31. 31.
    Nakhasi, H. L., Toews, A. D., andHorrocks, L. A. 1975. Effects of a postnatal protein deficiency on the content and composition of myelin from brains of weanling rats. Brain Res. 83:176–179.Google Scholar
  32. 32.
    Rajalakshmi, R., Kulkarni, A. B., andRamakrishnan, C. V. 1974. Effects of preweaning and post-weaning undernutrition on acetylcholine levels in rat brain. J. Neurochem. 23:119–121.PubMedGoogle Scholar
  33. 33.
    Culley, W. J., andMertz, E. T. 1965. Effect of restricted food intake on growth and composition of preweaning rat brain. Proc. Soc. Exp. Biol. Med. 118:233–235.PubMedGoogle Scholar
  34. 34.
    Reddy, P. V. andSastry, P. S. 1978. Effects of undernutrition on the metabolism of phospholipids and gangliosides in developing rat brain. Br. J. Nutr. 40:403–410.PubMedGoogle Scholar
  35. 35.
    Soukup, J. F., Friedel, R. O., andSchanberg, S. M. 1978. Microwave irradiation fixation for studies of polyphosphoinositide metabolism in brain. J. Neurochem. 30:635–637.PubMedGoogle Scholar
  36. 36.
    Soukup, J. F., Friedel, R. O., andSchanberg, S. M. 1978. Cholinergic stimulation of polyphosphoinositide metabolism in brain in vivo. Biochem. Pharmacol. 27:1239–1243.PubMedGoogle Scholar
  37. 37.
    Hauser, G., andEichberg, J. 1973. Improved conditions for the preservation and extraction of polyphosphoinositides. Biochim. Biophys. Acta 326:201–209.PubMedGoogle Scholar
  38. 38.
    Cragg, B. G. 1972. The development of cortical synapses during starvation in the rat. Brain 95:143–150.PubMedGoogle Scholar
  39. 39.
    Cordero, M. E., Diza, G., andAraya, J. 1976. Neocortex development during severe malnutrition in the rat. Am. J. Clin. Nutr. 29:358–365.PubMedGoogle Scholar
  40. 40.
    Pysh, J. J., Perkins, R. E., andBeck, L. S. 1979. The effect of postnatal undernutrition and the development of mouse Purkinje cell dendritic tree. Brain Res. 163:165–170.PubMedGoogle Scholar
  41. 41.
    Hammer, R. P., Jr. 1981. The influence of pre- and postnatal undernutrition on the developing brain stem reticular core, a quantitative Golgi study. Dev. Brain Res. 227:191–201.Google Scholar
  42. 42.
    Gambetti, P., Gambetti, A. L., Rizzute, N., Shafer, B., andPfaff, L. 1974. Synapses and malnutrition: Quantitative ultrastructural study of rat cerebral cortex. Exp. Neurol. 43:464–473.PubMedGoogle Scholar
  43. 43.
    Shoemaker, W. J., andBloom, F. E. 1977. Effect of undernutrition on brain morphology. Pages 147–192,in Wurtman, R. L. andWurtman J. J. (eds.), Nutrition and the Brain, Vol. 2, Raven Press, New York.Google Scholar
  44. 44.
    Hammer, R. P., Jr., andVan Marthens, E. 1981. Morphological development of the brain stem reticular core in prenatally undernourished rats. Dev. Brain Res. 227:203–212.Google Scholar
  45. 45.
    Wiggins, R. C., andFuller, G. N. 1978. Early postnatal starvation causes lasting brain hypomyelination. J. Neurochem. 30:1231–1237.PubMedGoogle Scholar
  46. 46.
    Reddy, P. V., Das, A., andSastry, P. S. 1979. Quantitative and compositional changes in myelin of undernourished and protein malnourished rat brain. Brain Res. 161:227–235.PubMedGoogle Scholar
  47. 47.
    Fox, J. H., Fishman, M. A., Dodge, P. R., andPrensky, A. L. 1972. The effects of malnutrition on human central nervous system myelin. Neurology 22:1213–1216.PubMedGoogle Scholar
  48. 48.
    Krigman, M. R., andHogan, E. L. 1976. Undernutrition in the developing rat: Effect upon myelination. Brain Res. 107:239–255.PubMedGoogle Scholar
  49. 49.
    Wiggins, R. C. 1982. Myelin development and nutritional insufficiency. Brain Res. Rev. 4:151–175.Google Scholar
  50. 50.
    Culley, W., Yuan, L., andMertz, E. 1966. Effect of food restriction and age on rat brain phospholipid levels. Fed. Proc. 25:674.Google Scholar
  51. 51.
    Simons, S. D., andJohnston, P. V. 1976. Prenatal and postnatal protein restriction in the rat: Effect on some parameters related to brain development and prospects for rehabilitation. J. Neurochem. 27:63–69.PubMedGoogle Scholar
  52. 52.
    Wiggins, R. C., Miller, S. L., Benjamins, J. A., Krigman, M. R., andMorell, P. 1976. Myelin synthesis during postnatal nutritional deprivation and subsequent rehabilitation. Brain Res. 107:257–273.PubMedGoogle Scholar
  53. 53.
    Downes, C. P. 1982. Receptor-stimulated inositol phospholipid metabolism in the central nervous system. Cell Calcium 3:413–428.PubMedGoogle Scholar
  54. 54.
    Nijjar, M. S., andHawthorne, J. N. 1977. Purification and properties of polyphosphoinositide phosphomonoesterase from rat brain. Biochim. Biophys. Acta 480:390–402.PubMedGoogle Scholar
  55. 55.
    Irvine, R. F., Letcher, A. J., andDawson, R. M. C. 1984. Phosphatidylinositol-4,5-bisphosphate phosphodiesterase and phosphomonoesterase activities of rat brain. Some properties and possible control mechanisms. Biochem. J. 218:177–185.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1986

Authors and Affiliations

  • Uma S. Ananth
    • 1
    • 2
  • C. V. Ramakrishnan
    • 4
  • George Hauser
    • 1
    • 3
    • 2
  1. 1.Ralph Lowell LaboratoriesMcLean HospitalBelmont
  2. 2.Department of Biological ChemistryHarvard Medical SchoolBoston
  3. 3.Department of PsychiatryHarvard Medical SchoolBoston
  4. 4.Biochemistry Department Faculty of ScienceM.S. University of BarodaBarodaIndia

Personalised recommendations