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PMID: 24275289 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Hippocampal mossy fiber leu-enkephalin immunoreactivity in female rats is significantly altered following both acute and chronic stress.

Journal of chemical neuroanatomy ·Vol. 55 ·2014-01-00 ·Pages 9-17

Pierce JP, Kelter DT, McEwen BS, Waters EM, Milner TA

Abstract

Research indicates that responses to stress are sexually dimorphic, particularly in regard to learning and memory processes: while males display impaired cognitive performance and hippocampal CA3 pyramidal cell dendritic remodeling following chronic stress, females exhibit enhanced performance and no remodeling. Leu-enkephalin, an endogenous opioid peptide found in the hippocampal mossy fiber pathway, plays a critical role in mediating synaptic plasticity at the mossy fiber-CA3 pyramidal cell synapse. Estrogen is known to influence the expression of leu-enkephalin in the mossy fibers of females, with leu-enkephalin levels being highest at proestrus and estrus, when estrogen levels are elevated. Since stress is also known to alter the expression of leu-enkephalin in various brain regions, this study was designed to determine whether acute or chronic stress had an effect on mossy fiber leu-enkephalin levels in females or males, through the application of correlated quantitative light and electron microscopic immunocytochemistry. Both acute and chronic stress eliminated the estrogen-dependence of leu-enkephalin levels across the estrous cycle in females, but had no effect on male levels. However, following acute stress leu-enkephalin levels in females were consistently lowered to values comparable to the lowest control values, while following chronic stress they were consistently elevated to values comparable to the highest control values. Ultrastructural changes in leu-enkephalin labeled dense core vesicles paralleled light microscopic observations, with acute stress inducing a decrease in leu-enkephalin labeled dense core vesicles, and chronic stress inducing an increase in leu-enkephalin labeled dense-core vesicles in females. These findings suggest that alterations in leu-enkephalin levels following stress could play an important role in the sex-specific responses that females display in learning processes, including those important in addiction.

Keywords
CA3 area Electron microscopy Estrogen Female Hippocampus Leu-enkephalin
MeSH Terms
Animals Dendrites/metabolism Enkephalin, Leucine/metabolism Estrous Cycle/metabolism Female Immunohistochemistry Male Mossy Fibers, Hippocampal/metabolism Rats Rats, Sprague-Dawley Sex Factors Stress, Physiological/physiology Stress, Psychological/metabolism
Chemicals
Enkephalin, Leucine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Pierce Joseph P
Brain and Mind Research Institute, Weill Cornell Medical College, 407 East 61st Street, New York, NY 10065, United States.
Kelter David T
Brain and Mind Research Institute, Weill Cornell Medical College, 407 East 61st Street, New York, NY 10065, United States.
McEwen Bruce S
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States.
Waters Elizabeth M
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States.
Milner Teresa A
Brain and Mind Research Institute, Weill Cornell Medical College, 407 East 61st Street, New York, NY 10065, United States; Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States. Electronic address: [email protected].
References (64)
64 references, click to expand
  1. Chronic stress alters synaptic terminal structure in hippocampus.
    Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):14002-8 PMID: 9391142
  2. Stress and the brain: from adaptation to disease.
    Nat Rev Neurosci. 2005 Jun;6(6):463-75 PMID: 15891777
  3. Repeated swim stress induces kappa opioid-mediated activation of extracellular signal-regulated kinase 1/2.
    Neuroreport. 2008 Sep 17;19(14):1417-22 PMID: 18766023
  4. Estrogen-induced changes in place and response learning in young adult female rats.
    Behav Neurosci. 2002 Jun;116(3):411-20 PMID: 12049322
  5. Tracking the estrogen receptor in neurons: implications for estrogen-induced synapse formation.
    Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7093-100 PMID: 11416193
  6. Effects of immobilization stress on neurochemical markers in the motivational system of the male rat.
    Brain Res. 2007 Jun 25;1155:108-15 PMID: 17511973
  7. Differential distribution in rat brain of mu opioid receptor carboxy terminal splice variants MOR-1C-like and MOR-1-like immunoreactivity: evidence for region-specific processing.
    J Comp Neurol. 2000 Apr 3;419(2):244-56 PMID: 10723002
  8. Kappa opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses.
    J Neurosci. 2003 Jul 2;23(13):5674-83 PMID: 12843270
  9. Peptidergic transmission: from morphological correlates to functional implications.
    Micron. 1996 Feb;27(1):35-91 PMID: 8756315
  10. Implications of CA3 NMDA and opiate receptors for spatial pattern completion in rats.
    Hippocampus. 2010 Apr;20(4):550-7 PMID: 19650123
  11. Long-term potentiation in direct perforant path projections to the hippocampal CA3 region in vivo.
    J Neurophysiol. 2002 Feb;87(2):669-78 PMID: 11826036
  12. Ovarian steroids alter mu opioid receptor trafficking in hippocampal parvalbumin GABAergic interneurons.
    Exp Neurol. 2009 Sep;219(1):319-27 PMID: 19505458
  13. Spatial learning of female mice: a role of the mineralocorticoid receptor during stress and the estrous cycle.
    Front Behav Neurosci. 2013 May 30;7:56 PMID: 23754993
  14. Mu opioid receptors are associated with the induction of hippocampal mossy fiber long-term potentiation.
    J Pharmacol Exp Ther. 1992 Nov;263(2):725-33 PMID: 1359112
  15. Ultrastructural basis for interactions between central opioids and catecholamines. I. Rostral ventrolateral medulla.
    J Neurosci. 1989 Jun;9(6):2114-30 PMID: 2566665
  16. Estrogen promotes stress sensitivity in a prefrontal cortex-amygdala pathway.
    Cereb Cortex. 2010 Nov;20(11):2560-7 PMID: 20139149
  17. Morphometry of a peptidergic transmitter system: dynorphin B-like immunoreactivity in the rat hippocampal mossy fiber pathway before and after seizures.
    Hippocampus. 1999;9(3):255-76 PMID: 10401641
  18. Role of endogenous opioid system in the regulation of the stress response.
    Prog Neuropsychopharmacol Biol Psychiatry. 2001 May;25(4):729-41 PMID: 11383975
  19. Sex differences in dendritic atrophy of CA3 pyramidal neurons in response to chronic restraint stress.
    Neuroscience. 1997 Dec;81(3):689-97 PMID: 9316021
  20. Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement.
    Neuroscience. 2000;97(2):253-66 PMID: 10799757
  21. Evidence for sex-specific shifting of neural processes underlying learning and memory following stress.
    Physiol Behav. 2010 Feb 9;99(2):204-11 PMID: 19376144
  22. Localization of enkephalin-like immunoreactivity to identified axonal and neuronal populations of the rat hippocampus.
    J Comp Neurol. 1981 May 10;198(2):335-50 PMID: 6263955
  23. Exocytosis from neuronal large dense-cored vesicles.
    Int Rev Cytol. 1990;121:67-126 PMID: 1972143
  24. Induction and adaptation of Fos expression in the rat brain by two types of acute restraint stress.
    Brain Res Bull. 2000 Jun;52(3):171-82 PMID: 10822158
  25. Sex differences in spatial and non-spatial Y-maze performance after chronic stress.
    Neurobiol Learn Mem. 2003 Jan;79(1):32-40 PMID: 12482677
  26. Estrogen actions in the central nervous system.
    Endocr Rev. 1999 Jun;20(3):279-307 PMID: 10368772
  27. Chronic stress and neural function: accounting for sex and age.
    J Neuroendocrinol. 2007 Oct;19(10):743-51 PMID: 17850456
  28. Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats.
    Neuroscience. 2002;113(2):401-10 PMID: 12127097
  29. Enkephalin release into the ventral tegmental area in response to stress: modulation of mesocorticolimbic dopamine.
    Brain Res. 1987 Jun 30;414(2):339-48 PMID: 3620936
  30. Cyclic changes in estradiol regulate synaptic plasticity through the MAP kinase pathway.
    Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13391-5 PMID: 11687663
  31. The neurobiology of stress: from serendipity to clinical relevance.
    Brain Res. 2000 Dec 15;886(1-2):172-189 PMID: 11119695
  32. Special axo-dendritic synapses in the hippocampal cortex: electron and light microscopic studies on the layer of mossy fibers.
    J Comp Neurol. 1961 Oct;117:133-59 PMID: 13869693
  33. Estrous cycle and sex differences in performance on anxiety tasks coincide with increases in hippocampal progesterone and 3alpha,5alpha-THP.
    Pharmacol Biochem Behav. 2000 Nov;67(3):587-96 PMID: 11164090
  34. Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters.
    Horm Behav. 1998 Oct;34(2):149-62 PMID: 9799625
  35. Ovarian steroidal control of connectivity in the female hippocampus: an overview of recent experimental findings and speculations on its functional consequences.
    Hippocampus. 1997;7(2):239-45 PMID: 9136053
  36. Corticosteroids and the brain.
    J Steroid Biochem Mol Biol. 1990 Nov 20;37(3):387-94 PMID: 2257242
  37. The influences of reproductive status and acute stress on the levels of phosphorylated mu opioid receptor immunoreactivity in rat hippocampus.
    Front Endocrinol (Lausanne). 2011 Aug 19;2(18): PMID: 22468144
  38. Ovarian steroids modulate leu-enkephalin levels and target leu-enkephalinergic profiles in the female hippocampal mossy fiber pathway.
    Brain Res. 2008 Sep 26;1232:70-84 PMID: 18691558
  39. Stress differentially alters mu opioid receptor density and trafficking in parvalbumin-containing interneurons in the female and male rat hippocampus.
    Synapse. 2013 Nov;67(11):757-72 PMID: 23720407
  40. Hormonal regulation of delta opioid receptor immunoreactivity in interneurons and pyramidal cells in the rat hippocampus.
    Neurobiol Learn Mem. 2011 Feb;95(2):206-20 PMID: 21224009
  41. Parvalbumin-containing fast-spiking basket cells generate the field potential oscillations induced by cholinergic receptor activation in the hippocampus.
    J Neurosci. 2010 Nov 10;30(45):15134-45 PMID: 21068319
  42. Estrogen facilitates induction of long term potentiation in the hippocampus of awake rats.
    Brain Res. 1997 Dec 19;778(2):430-8 PMID: 9459564
  43. A model of hippocampal memory encoding and retrieval: GABAergic control of synaptic plasticity.
    Trends Neurosci. 1998 Jul;21(7):273-8 PMID: 9683315
  44. Characterization of the prodynorphin and proenkephalin neuropeptide systems in rat hippocampus.
    J Neurosci. 1985 Mar;5(3):808-16 PMID: 3838345
  45. Ultrastructural heterogeneity of enkephalin-containing terminals in the rat hippocampal formation.
    J Comp Neurol. 1995 Jul 31;358(3):324-42 PMID: 7560290
  46. LTP varies across the estrous cycle: enhanced synaptic plasticity in proestrus rats.
    Brain Res. 1995 Dec 12;703(1-2):26-30 PMID: 8719612
  47. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures.
    J Histochem Cytochem. 1981 Apr;29(4):577-80 PMID: 6166661
  48. Gender-dependent alterations in corticosteroid receptor status and spatial performance following 21 days of restraint stress.
    Neuroscience. 2004;125(1):47-55 PMID: 15051144
  49. Sex and estrogen receptor expression influence opioid peptide levels in the mouse hippocampal mossy fiber pathway.
    Neurosci Lett. 2013 Sep 27;552:66-70 PMID: 23933204
  50. Estrogen increases the number of spinophilin-immunoreactive spines in the hippocampus of young and aged female rhesus monkeys.
    J Comp Neurol. 2003 Oct 27;465(4):540-50 PMID: 12975814
  51. Opioid systems in the dentate gyrus.
    Prog Brain Res. 2007;163:245-63 PMID: 17765723
  52. Acute footshock-stress increases spatial learning-memory and correlates to increased hippocampal BDNF and VEGF and cell numbers in adolescent male and female rats.
    Neurosci Lett. 2012 Apr 18;514(2):141-6 PMID: 22426107
  53. Hippocampal formation: shedding light on the influence of sex and stress on the brain.
    Brain Res Rev. 2007 Oct;55(2):343-55 PMID: 17395265
  54. Neurons with mu opioid receptors interact indirectly with enkephalin-containing neurons in the rat dentate gyrus.
    Exp Neurol. 2002 Jul;176(1):254-61 PMID: 12093103
  55. Quantitative light microscopic demonstration of increased pallidal and striatal met5-enkephalin-like immunoreactivity in rats following chronic treatment with haloperidol but not with clozapine: implications for the pathogenesis of neuroleptic-induced movement disorders.
    Exp Neurol. 1992 Jul;117(1):17-27 PMID: 1618284
  56. Neuropeptide signaling near and far: how localized and timed is the action of neuropeptides in brain circuits?
    Invert Neurosci. 2009 Nov;9(2):57-75 PMID: 19756790
  57. The influences of reproductive status and acute stress on the levels of phosphorylated delta opioid receptor immunoreactivity in rat hippocampus.
    Brain Res. 2013 Jun 26;1518:71-81 PMID: 23583481
  58. Endogenous opioid regulation of hippocampal function.
    Int Rev Neurobiol. 1996;39:145-96 PMID: 8894847
  59. Acute predator stress impairs the consolidation and retrieval of hippocampus-dependent memory in male and female rats.
    Learn Mem. 2008 Apr 07;15(4):271-80 PMID: 18391188
  60. Stress and hippocampal plasticity.
    Annu Rev Neurosci. 1999;22:105-22 PMID: 10202533
  61. Gonadal hormones are responsible for maintaining the integrity of spine synapses in the CA1 hippocampal subfield of female nonhuman primates.
    J Comp Neurol. 2002 May 20;447(1):34-42 PMID: 11967893
  62. Degenerating processes identified by electron microscopic immunocytochemical methods.
    Methods Mol Biol. 2011;793:23-59 PMID: 21913092
  63. Estrogen improves performance of reinforced T-maze alternation and prevents the amnestic effects of scopolamine administered systemically or intrahippocampally.
    Neurobiol Learn Mem. 1998 May;69(3):225-40 PMID: 9707487
  64. Endogenous activation of mu and delta-1 opioid receptors is required for long-term potentiation induction in the lateral perforant path: dependence on GABAergic inhibition.
    J Neurosci. 1996 Dec 15;16(24):8123-31 PMID: 8987837
Article Info
Journal
Journal of chemical neuroanatomy
Abbr.
J Chem Neuroanat
ISSN
1873-6300
Published
2014-01-00
Epub
2013-00-22
Pages
9-17
Language
English
Region
Netherlands
NLM ID
8902615
PMCID
PMC4225781
Subset
IM
Grants
NINDS NIH HHS · R01 NS007080 · United States
NIA NIH HHS · R21 AG039850 · United States
NINDS NIH HHS · NS007080 · United States
NIDA NIH HHS · R01 DA008259 · United States
NIA NIH HHS · AG039850 · United States
NHLBI NIH HHS · P01 HL096571 · United States
NIDDK NIH HHS · DK07313 · United States
NIDA NIH HHS · DA08259 · United States
NHLBI NIH HHS · HL096571 · United States
NHLBI NIH HHS · R01 HL098351 · United States
NIDDK NIH HHS · T32 DK007313 · United States
NHLBI NIH HHS · HL098351 · United States
NIA NIH HHS · P01 AG016765 · United States
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