Skip to main content
Log in

The Response to Postnatal Stress: Amino Acids Transporters and PKC Activity

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

It is well known that animals exposed to stressful stimuli during their early life develop different neurological disorders when they become adults. In this study, we evaluated the effect of acute cold stress on γ-aminobutyric acid (GABA) and L-Serine (L-Ser) transporters in vitro, using the uptake of [3H]-GABA and [3H]L-Ser by synaptosomes-enriched fractions isolated from rat cerebral cortex during postnatal development. GABA and L-Ser uptake studies in vitro will be used in this investigation as a colateral evidence of changes in the expression of transporters of GABA and L-Ser. We observed that the maximum velocity (V max) in L-Ser and GABA uptake after stress session increased in all stages studied. In contrast, K m values of L-Ser uptake enhancent in almost age calculated, excluding at PD21 after cold stress during development, at the same time as K m (uptake affinity) values of GABA increased in just about age considered but not at PD5 compared with the control group. Finally we investigated the mechanism by which cells regulate the substrate affinity of L-Ser and GABA transporters. We demonstrated a significantly increase in total PKC activity to PD5 from PD21. Pretreatment with PKC inhibitor: staurosporine (SP) led to a restoration of control uptake in several postnatal-days suggesting a relationship between amino acids system and PKC activation. These findings suggest that a single exposure to postnatal cold stress at different periods after birth modifies both GABA and L-Ser transporters and the related increase in total PKC activity could be intracellular events that participate in neuronal plasticity by early life stress, which could be relevant to function of transporters in the adult rat brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Heim C, Nemeroff CB (2002) Neurobiology of early life stress: clinical studies. Semin Clin Neuropsychiatry 7:147–159

    Article  PubMed  Google Scholar 

  2. Kaufman J, Plotsky PM, Nemeroff CB et al (2000) Effects of early adverse experiences on brain structure and function: clinical implications. Biol Psychiatry 48:778–790

    Article  CAS  PubMed  Google Scholar 

  3. Gutman DA, Nemeroff CB (2002) Neurobiology of early life stress: rodent studies. Semin Clin Neuropsychiatry 7(2):89–95

    Article  PubMed  Google Scholar 

  4. Ganguly K, Schinder AF, Wong ST et al (2001) GABA itself promotes the development switch of neuronal GABAergic responses from excitation to inhibition. Cell 105:521–532

    Article  CAS  PubMed  Google Scholar 

  5. Ben-Ari Y (2002) Excitatory actions of GABA during development: the nature of the nurture. Nat Rev Neurosci 3:728–739

    Article  CAS  PubMed  Google Scholar 

  6. Yamada J, Okabe A, Toyoda H et al (2004) Cl uptake promoting depolarizing GABA actions in immature rat neocortical neurons is mediated by NKCC1. J Physiol 557:829–841

    Article  CAS  PubMed  Google Scholar 

  7. Rivera C, Voipio J, Payne JA et al (1999) The K+/Cl–co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397:251–255

    Article  CAS  PubMed  Google Scholar 

  8. Rivera C, Voipio J, Kaila K (2005) Two developmental switches in GABAergic signalling: the K+-Cl cotransporter KCC2 and carbonic anhydrase CAVII. J Physiol 562:27–36

    Article  CAS  PubMed  Google Scholar 

  9. Tyzio R, Minlebaev M, Rheims S et al (2008) Postnatal changes in somatic γ-aminobutyric acid signalling in the rat hippocampus. Eur J Neurosci 27(10):2515–2528

    Article  PubMed  Google Scholar 

  10. Conti F, Minelli A, Melone M (2004) GABA transporters in mammalian cerebral cortex: localization, development and pathological implications. Brain Res Rev 45:196–212

    Article  CAS  PubMed  Google Scholar 

  11. Wonders CP, Anderson SA (2006) The origin and specification of cortical interneurons. Nature Rev Neurosci 7:687–696

    Article  CAS  Google Scholar 

  12. Mitoma J, Furuya S, Hirabayashi Y (1998) A novel metabolic communication between neurons and astrocytes: non-essential amino acid L-serine released from astrocytes is essential for developing hippocampal neurons. Neurosc Res 30:195–199

    Article  CAS  Google Scholar 

  13. Furuya S, Tabata T, Mitoma J et al (2000) L-serine serve as major astroglia-derived trophic factors for cerebelar Purkinje neurons. Proc Natl Acad Sci USA 97:11528–11533

    Article  CAS  PubMed  Google Scholar 

  14. Snell K (1984) Enzymes of serine metabolism in normal, developing and neoplastic rat tissues. Adv Enzyme Regul 22:325–400

    Article  CAS  PubMed  Google Scholar 

  15. Snyder SH, Kim PM (2000) D-amino acids as putative neurotransmitters: focus on D-serine. Neurochem Res 25:553–560

    Article  CAS  PubMed  Google Scholar 

  16. de Koning TJ, Snell K, Duran M, Berger R, Poll-The BT, Surtees R (2003) L-Serine in disease and development. Biochem J 371:653–661

    Article  PubMed  Google Scholar 

  17. Scolari MJ, Acosta GB (2007) D-serine a new word in the glutamatergic neuro-glial language. Amino Acids 33:563–574

    Article  CAS  PubMed  Google Scholar 

  18. Savoca R, Ziegler U, Sonderegger P (1995) Effects of L-serine on neurons in vitro. J Neurosci Meth 61:159–167

    Article  CAS  Google Scholar 

  19. Yamamoto T, Nishizaki I, Furuya S et al (2003) Characterization of rapid and high-affinity uptake of L-serine in neurons and astrocytes in primary culture. FEBS Lett 548:69–73

    Article  CAS  PubMed  Google Scholar 

  20. Takarada T, Balcar VJ, Baba K, Takamoto A et al (2003) Uptake of [3H] L-Serine in rat brain synaptosomal fractions. Brain Res 983:36–47

    Article  CAS  PubMed  Google Scholar 

  21. Acosta GB, Takarada T, Yoneda Y (2005) L-serine in the brain, chapter 2. In: Yoneda Y (Ed) Amino acids signaling 04, 2005. Research Signpost, Kerala, India, pp 17–31

  22. Evans JE, Frostholm A, Rotter A (1996) Embryonic and postnatal expression of four gamma-aminobutyric acid transporter mRNAs in the mouse brain and leptomeninges. J Comp Neurol 376:431–446

    Article  CAS  PubMed  Google Scholar 

  23. Minelli A, Barbaresi P, Conti F (2003) Postnatal developmentof high-affinity plasma membrane GABA transporters GAT-2 and GAT-3 in the rat cerebral cortex. Brain Res Dev BrainRes 2003;142:7–18. Erratum in: Brain Res Dev Brain Res 145:167–1678

    Article  CAS  Google Scholar 

  24. Wong PT-H, McGeer EG (1981) Postnatal changes of GABAergic and glutamatergic parameters. Dev Brain Res 1:519–529

    Article  CAS  Google Scholar 

  25. Utsunomiya-Tate N, Endou H, Kanai Y (1996) Cloning and functional characterization of a system ASC-like Na+-dependent neutral amino acid transporter. J Biol Chem. 271:14883–14890

    Article  CAS  PubMed  Google Scholar 

  26. Shafqat S, Tamarappoo BK, Kilberg MS, Puranam RS, McNamara JO, Guadaño-Ferraz A, Fremeau RT Jr (1993) Cloning and expression of a novel Na(+)-dependent neutral amino acid transporter structurally related to mammalian Na+/glutamate cotransporters. J Biol Chem 268:15351–15355

    CAS  PubMed  Google Scholar 

  27. Kekuda R, Prasad PD, Fei YJ, Torres-Zamorano V, Sinha S, Yang-Feng TL, Leibach FH, Ganapathy V (1996) Cloning of the sodium-dependent, broad-scope, neutral amino acid transporter Bo from a human placental choriocarcinoma cell line. J Biol Chem 271:18657–18661

    Article  CAS  PubMed  Google Scholar 

  28. Corey JL, Davidson N, Lester HA et al (1994) Protein kinase C modulates the activity of a cloned gamma-aminobutyric acid transporter expressed in Xenopus oocytes via regulated subcellular redistribution of the transporter. J Biol Chem 269:14759–14767

    CAS  PubMed  Google Scholar 

  29. Robinson MB (2002) Regulated trafficking of neurotransmitter transporters: common notes but different melodies. J Neurochem 80:1–11

    Article  CAS  PubMed  Google Scholar 

  30. Kalandadze A, Wu Y, Robinson MB (2002) Protein kinase C activation decreases cell surface expression of the GLT-1 subtype of glutamate transporter. Requirement of a carboxyl-terminal domain and partial dependence on serine 486. J Biol Chem 277:45741–45750

    Article  CAS  PubMed  Google Scholar 

  31. Quick MW, Hu J, Wang D et al (2004) Regulation of a gamma-aminobutyric acid transporter by reciprocal tyrosine and serine phosphorylation. J Biol Chem 279:15961–15967

    Article  CAS  PubMed  Google Scholar 

  32. Way KJ, Chou E, King GL (2000) Identification of PKC-isoform-specific biological actions using pharmacological approaches. Trends Pharmacol Sci 21:181–187

    Article  CAS  PubMed  Google Scholar 

  33. Nishizuka Y (1992) Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258:607–614

    Article  CAS  PubMed  Google Scholar 

  34. Nishizuka Y (1998) The molecular heterogeneity of protein kinase C and its implication for cellular regulation. Nature 334:661–665

    Article  Google Scholar 

  35. Casabona G (1997) Intracellular signal modulation: a pivotal role for protein kinase C. Prog Neuropsychopharmacol Biol Psychiatry 21:407–425

    Article  CAS  PubMed  Google Scholar 

  36. Glowinski J, Iversen LL (1996) Regional studies of catecholamines in rat brain. I. The disposition of 3H-noradrenaline, 3H-dopamine and 3H- DOPAC in various regions of the brain. J. Neurochem 13:665–669

    Google Scholar 

  37. Balcar VJ, Johnston GAR (1972) The structural specificity of the high affinity uptake of L-glutamate and L-aspartate by rat brain slices. J Neurochem 19:2657–2666

    Article  CAS  PubMed  Google Scholar 

  38. Lowry OH, Rosebrough NJ, Farr AI et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  39. Genaro AM, Bosca L (1993) Early signals in alloantigen induced B-cell proliferation. Comparison between B-cell triggering by intact allogeneic cell and solubilized alloantigen. J Immunol 151:1832–1843

    CAS  PubMed  Google Scholar 

  40. Retana-Márquez S, Bonilla-Jaime H, Vázquez-Palacios G et al (2003) Body weight gain and diurnal differences of corticosterone changes in response to acute and chronic stress in rats. Psychoneuroendocrinology 28:207–227

    Article  PubMed  Google Scholar 

  41. Winner BJ (1971) Statistical principles in experimental design. New York, Mc Graw Hill

    Google Scholar 

  42. Landeira-Fernández J (2004) Analysis of the cold-water restraint procedure in gastric ulceration and body temperature. Physiol Behav 82:827–833

    PubMed  Google Scholar 

  43. Cheluja MG, Scolari MJ, Coelho TM et al (2007) L-serine and GABA uptake by synaptosomes during postnatal development of rat. Comp Biochem Physiol A Mol Integr Physiol 146:499–505

    Article  PubMed  Google Scholar 

  44. Krnjevic K (1997) Role of GABA in cerebral cortex. Can J Physiol Pharm 75:439–451

    Article  CAS  Google Scholar 

  45. Nguyen L, Rigo JM, Rocher V et al (2001) Neurotransmitters as early signals for central nervous system development. Cell Tissue Res 305:187–202

    Article  CAS  PubMed  Google Scholar 

  46. Kim PM, Aizawa H, Kim PS et al (2005) Serine racemase: activation by glutamate neurotransmission via glutamate receptor interacting protein and mediation of neuronal migration. Proc Natl Acad Sci USA 102:2105–2110

    Article  CAS  PubMed  Google Scholar 

  47. Salatino AE, Odeón MM, Orta MM, Acosta GB (2009) The effects of repeated early maternal separation and cold stress on brain development. First Joint Meeting of the Argentine Society for Neurosciences (SAN) & the Argentine Workshop in Neurosciences (TAN) IRCN 295

  48. Herlenius E, Lagercrantz H (2004) Development of neurotransmitter systems during critical periods. Exp Neurol 190(Suppl 1):S8–S21

    Article  CAS  PubMed  Google Scholar 

  49. Schell MJ (2004) The N-methyl-D-aspartate receptor glycine site and D-serine metabolism: an evolutionary perspective. Phil Trans R Soc Lond 359:943–964

    Article  CAS  Google Scholar 

  50. Guillet BA, Velly LJ, Canolle B et al (2005) Differential regulation by protein kinases of activity and cell surface expression of glutamate transporters in neuron-enriched cultures. Neurochem Int 46:337–346

    Article  CAS  PubMed  Google Scholar 

  51. Acosta GB, Otero Losada ME, Rubio MC (1993) Area-dependent changes in GABAergic function after acute and chronic cold stress. Neurosc Lett 154:175–178

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We wisk to thank to Ms Claudia García Bonelli and Ms Lidia Caballero for their helpful technique assistance with HPLC. This work was supported in part by grants B019 from the University of Buenos Aires and PIP 5869 from CONICET to GBA. GBA is member of CONICET.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gabriela Beatriz Acosta.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Odeon, M.M., Salatino, A.E., Rodríguez, C.B. et al. The Response to Postnatal Stress: Amino Acids Transporters and PKC Activity. Neurochem Res 35, 967–975 (2010). https://doi.org/10.1007/s11064-010-0153-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-010-0153-z

Keywords

Navigation