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Estradiol reduces dendritic spine density in the ventral striatum of female Syrian hamsters

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Abstract

Estradiol affects a variety of brain regions by modulating physiological and cellular functions as well as neuronal morphology. Within the striatum, estradiol is known to induce physiological and molecular changes, yet estradiol’s effects on striatal dendritic morphology have not yet been evaluated. Using ballistic delivery of the lipophilic dye DiI to tissue sections, we were able to evaluate estradiol’s effects on striatal morphology in female Syrian hamsters. We found that estradiol significantly decreased spine density within the nucleus accumbens core, with no effect in the nucleus accumbens shell or caudate. Interestingly, estradiol treatment caused a significant deconstruction of spines from more to less mature spine subtypes in both the nucleus accumbens core and shell regardless of changes in spine density. These results are significant in that they offer a novel mechanism for estradiol actions on a wide variety of nucleus accumbens functions such as motivation or reward as well as their pathological consequences (e.g. drug addiction).

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References

  • Anwyl R (1999) Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Res Brain Res Rev 29:83–120

    Article  CAS  PubMed  Google Scholar 

  • Becker JB (2000) Oestrogen effects on dopaminergic function in striatum. Novartis Found Symp 230:134–145; discussion 145–154

    Google Scholar 

  • Becker JB, Hu M (2008) Sex differences in drug abuse. Front Neuroendocrinol 29:36–47

    Article  CAS  PubMed  Google Scholar 

  • Bourque M, Dluzen DE, Di Paolo T (2009) Neuroprotective actions of sex steroids in Parkinson’s disease. Front Neuroendocrinol 30:142–157

    Article  CAS  PubMed  Google Scholar 

  • Bradley KC, Haas AR, Meisel RL (2005) 6-Hydroxydopamine lesions in female hamsters (Mesocricetus auratus) abolish the sensitized effects of sexual experience on copulatory interactions with males. Behav Neurosci 119:224–232

    Article  CAS  PubMed  Google Scholar 

  • Calizo LH, Flanagan-Cato LM (2000) Estrogen selectively regulates spine density within the dendritic arbor of rat ventromedial hypothalamic neurons. J Neurosci 20:1589–1596

    CAS  PubMed  Google Scholar 

  • Calizo LH, Flanagan-Cato LM (2002) Estrogen-induced dendritic spine elimination on female rat ventromedial hypothalamic neurons that project to the periaqueductal gray. J Comp Neurol 447:234–248

    Article  CAS  PubMed  Google Scholar 

  • Chen JC, Chen PC, Chiang YC (2009) Molecular mechanisms of psychostimulant addiction. Chang Gung Med J 32:148–154

    PubMed  Google Scholar 

  • Cooke BM, Woolley CS (2005) Gonadal hormone modulation of dendrites in the mammalian CNS. J Neurobiol 64:34–46

    Article  CAS  PubMed  Google Scholar 

  • Cyr M, Calon F, Morissette M, Di Paolo T (2002) Estrogenic modulation of brain activity: implications for schizophrenia and Parkinson’s disease. J Psychiatry Neurosci 27:12–27

    PubMed  Google Scholar 

  • de Castilhos J, Forti CD, Achaval M, Rasia-Filho AA (2008) Dendritic spine density of posterodorsal medial amygdala neurons can be affected by gonadectomy and sex steroid manipulations in adult rats: a Golgi study. Brain Res 1240:73–81

    Article  PubMed  Google Scholar 

  • Donahue JE, Stopa EG, Chorsky RL, King JC, Schipper HM, Tobet SA, Blaustein JD, Reichlin S (2000) Cells containing immunoreactive estrogen receptor-alpha in the human basal forebrain. Brain Res 856:142–151

    Article  CAS  PubMed  Google Scholar 

  • Ferraguti F, Shigemoto R (2006) Metabotropic glutamate receptors. Cell Tissue Res 326:483–504

    Article  CAS  PubMed  Google Scholar 

  • Frankfurt M, Gould E, Woolley CS, McEwen BS (1990) Gonadal steroids modify dendritic spine density in ventromedial hypothalamic neurons: a Golgi study in the adult rat. Neuroendocrinology 51:530–535

    Article  CAS  PubMed  Google Scholar 

  • Gan WB, Grutzendler J, Wong WT, Wong RO, Lichtman JW (2000) Multicolor “DiOlistic” labeling of the nervous system using lipophilic dye combinations. Neuron 27:219–225

    Article  CAS  PubMed  Google Scholar 

  • Gan WB, Grutzendler J, Wong RO, Lichtman JW (2009) Ballistic delivery of dyes for structural and functional studies of the nervous system. Cold Spring Harb Protoc (pdb.prot5202)

  • Grove-Strawser D, Boulware MI, Mermelstein PG (2010) Membrane estrogen receptors activate the metabotropic glutamate receptors mGluR5 and mGluR3 to bidirectionally regulate CREB phosphorylation in female rat striatal neurons. Neuroscience 140:1045–1055

    Google Scholar 

  • Hao J, Rapp PR, Leffler AE, Leffler SR, Janssen WG, Lou W, McKay H, Roberts JA, Wearne SL, Hof PR, Morrison JH (2006) Estrogen alters spine number and morphology in prefrontal cortex of aged female rhesus monkeys. J Neurosci 26:2571–2578

    Article  CAS  PubMed  Google Scholar 

  • Harris KM, Jensen FE, Tsao B (1992) Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation. J Neurosci 12:2685–2705

    CAS  PubMed  Google Scholar 

  • Hedges VL, Chakravarty S, Nestler EJ, Meisel RL (2009) Delta FosB overexpression in the nucleus accumbens enhances sexual reward in female Syrian hamsters. Genes Brain Behav 8:442–449

    Article  CAS  PubMed  Google Scholar 

  • Hering H, Sheng M (2001) Dendritic spines: structure, dynamics and regulation. Nat Rev Neurosci 2:880–888

    Article  CAS  PubMed  Google Scholar 

  • Kelley AE, Domesick VB (1982) The distribution of the projection from the hippocampal formation to the nucleus accumbens in the rat: an anterograde- and retrograde-horseradish peroxidase study. Neuroscience 7:2321–2335

    Article  CAS  PubMed  Google Scholar 

  • Korol DL (2004) Role of estrogen in balancing contributions from multiple memory systems. Neurobiol Learn Mem 82:309–323

    Article  CAS  PubMed  Google Scholar 

  • Kourrich S, Rothwell PE, Klug JR, Thomas MJ (2007) Cocaine experience controls bidirectional synaptic plasticity in the nucleus accumbens. J Neurosci 27:7921–7928

    Article  CAS  PubMed  Google Scholar 

  • McEwen B (2002) Estrogen actions throughout the brain. Recent Prog Horm Res 57:357–384

    Article  CAS  PubMed  Google Scholar 

  • McKinney RA, Capogna M, Durr R, Gahwiler BH, Thompson SM (1999) Miniature synaptic events maintain dendritic spines via AMPA receptor activation. Nat Neurosci 2:44–49

    Article  CAS  PubMed  Google Scholar 

  • Meisel RL, Mullins AJ (2006) Sexual experience in female rodents: cellular mechanisms and functional consequences. Brain Res 1126:56–65

    Article  CAS  PubMed  Google Scholar 

  • Meredith GE, Agolia R, Arts MP, Groenewegen HJ, Zahm DS (1992) Morphological differences between projection neurons of the core and shell in the nucleus accumbens of the rat. Neuroscience 50:149–162

    Article  CAS  PubMed  Google Scholar 

  • Mermelstein PG, Becker JB, Surmeier DJ (1996) Estradiol reduces calcium currents in rat neostriatal neurons via a membrane receptor. J Neurosci 16:595–604

    CAS  PubMed  Google Scholar 

  • Morissette M, Le Saux M, D’Astous M, Jourdain S, Al Sweidi S, Morin N, Estrada-Camarena E, Mendez P, Garcia-Segura LM, Di Paolo T (2008) Contribution of estrogen receptors alpha and beta to the effects of estradiol in the brain. J Steroid Biochem Mol Biol 108:327–338

    Article  CAS  PubMed  Google Scholar 

  • Mukai H, Tsurugizawa T, Murakami G, Kominami S, Ishii H, Ogiue-Ikeda M, Takata N, Tanabe N, Furukawa A, Hojo Y, Ooishi Y, Morrison JH, Janssen WG, Rose JA, Chambon P, Kato S, Izumi S, Yamazaki T, Kimoto T, Kawato S (2007) Rapid modulation of long-term depression and spinogenesis via synaptic estrogen receptors in hippocampal principal neurons. J Neurochem 100:950–967

    Article  CAS  PubMed  Google Scholar 

  • O’Brien JA, Holt M, Whiteside G, Lummis SC, Hastings MH (2001) Modifications to the hand-held Gene Gun: improvements for in vitro biolistic transfection of organotypic neuronal tissue. J Neurosci Methods 112:57–64

    Article  PubMed  Google Scholar 

  • O’Donnell P, Grace AA (1995) Synaptic interactions among excitatory afferents to nucleus accumbens neurons: hippocampal gating of prefrontal cortical input. J Neurosci 15:3622–3639

    PubMed  Google Scholar 

  • Robinson TE, Kolb B (2004) Structural plasticity associated with exposure to drugs of abuse. Neuropharmacology 47(Suppl 1):33–46

    Article  CAS  PubMed  Google Scholar 

  • Schikorski T, Stevens CF (1997) Quantitative ultrastructural analysis of hippocampal excitatory synapses. J Neurosci 17:5858–5867

    CAS  PubMed  Google Scholar 

  • Schoepp DD (2001) Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system. J Pharmacol Exp Ther 299:12–20

    CAS  PubMed  Google Scholar 

  • Sesack SR, Deutch AY, Roth RH, Bunney BS (1989) Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: an anterograde tract-tracing study with Phaseolus vulgaris leucoagglutinin. J Comp Neurol 290:213–242

    Article  CAS  PubMed  Google Scholar 

  • Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl) 168:3–20

    Article  CAS  Google Scholar 

  • Shen HW, Toda S, Moussawi K, Bouknight A, Zahm DS, Kalivas PW (2009) Altered dendritic spine plasticity in cocaine-withdrawn rats. J Neurosci 29:2876–2884

    Article  CAS  PubMed  Google Scholar 

  • Skynner MJ, Sim JA, Herbison AE (1999) Detection of estrogen receptor alpha and beta messenger ribonucleic acids in adult gonadotropin-releasing hormone neurons. Endocrinology 140:5195–5201

    Article  CAS  PubMed  Google Scholar 

  • Szego EM, Kekesi KA, Szabo Z, Janaky T, Juhasz GD (2010) Estrogen regulates cytoskeletal flexibility, cellular metabolism and synaptic proteins: a proteomic study. Psychoneuroendocrinology 35:807–819

    Article  CAS  PubMed  Google Scholar 

  • Tamaru Y, Nomura S, Mizuno N, Shigemoto R (2001) Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS: differential location relative to pre- and postsynaptic sites. Neuroscience 106:481–503

    Article  CAS  PubMed  Google Scholar 

  • Tunez I, Collado JA, Medina FJ, Pena J, Del CMM, Jimena I, Franco F, Rueda I, Feijoo M, Muntane J, Montilla P (2006) 17 beta-Estradiol may affect vulnerability of striatum in a 3-nitropropionic acid-induced experimental model of Huntington’s disease in ovariectomized rats. Neurochem Int 48:367–373

    Article  CAS  PubMed  Google Scholar 

  • Walf AA, Frye CA (2008) Rapid and estrogen receptor beta mediated actions in the hippocampus mediate some functional effects of estrogen. Steroids 73:997–1007

    Article  CAS  PubMed  Google Scholar 

  • Wang XB, Zhou Q (2010) Spine remodeling and synaptic modification. Mol Neurobiol 41:29–41

    Article  PubMed  Google Scholar 

  • Woolley CS (1998) Estrogen-mediated structural and functional synaptic plasticity in the female rat hippocampus. Horm Behav 34:140–148

    Article  CAS  PubMed  Google Scholar 

  • Woolley CS, Cohen RS (2002) Sex steroids and neuronal growth in adulthood. In: Pfaff DW, Arnold AA, Etgen AM, Fahrbach SE, Rubin RT (eds) Hormones brain and behavior, vol 4. Elsevier Science, San Diego, pp 717–777

  • Woolley CS, McEwen BS (1993) Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J Comp Neurol 336:293–306

    Article  CAS  PubMed  Google Scholar 

  • Woolley CS, Gould E, Frankfurt M, McEwen BS (1990) Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. J Neurosci 10:4035–4039

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by National Institutes of Health grant DA 13680 to RLM, and training grant T32 DA07234 (Virginia Seybold, PI).

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Correspondence to Nancy A. Staffend.

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Staffend, N.A., Loftus, C.M. & Meisel, R.L. Estradiol reduces dendritic spine density in the ventral striatum of female Syrian hamsters. Brain Struct Funct 215, 187–194 (2011). https://doi.org/10.1007/s00429-010-0284-7

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