title: Estradiol regulates large dense core vesicles in the hippocampus of adult female rats.
abstract: Previous work has shown that the steroid hormone estradiol facilitates the release of anticonvulsant neuropeptides from inhibitory neurons in the hippocampus to suppress seizures. Because neuropeptides are packaged in large dense core vesicles, estradiol may facilitate neuropeptide release through regulation of dense core vesicles. In the current study, we used serial section electron microscopy in the hippocampal CA1 region of adult female rats to test three hypotheses about estradiol regulation of dense core vesicles: (1) Estradiol increases the number of dense core vesicles in axonal boutons, (2) Estradiol increases the size of dense core vesicles in axonal boutons, (3) Estradiol shifts the location of dense core vesicles toward the periphery of axonal boutons, potentially lowering the threshold for neuropeptide release during seizures. We found that estradiol increases the number and size of dense core vesicles in inhibitory axonal boutons, consistent with increased neuropeptide content, but does not shift the location of dense core vesicles closer to the bouton periphery. These effects were specific to large dense core vesicles (>80 nm) in inhibitory boutons. Estradiol had no effects on small dense core vesicles or dense core vesicles in excitatory boutons. Our results indicate that estradiol suppresses seizures at least in part by increasing the potentially releasable pool of neuropeptides in the hippocampus, and that estradiol facilitation of neuropeptide release involves a mechanism other than mobilization of dense core vesicles toward sites of release.
authors.affiliation: Department of Neurobiology, Northwestern University, 2205 Tech Drive, Evanston, IL, 60208, USA.
authors.forename: Renee M
authors.initials: RM
authors.lastname: May
authors.forename: Nino
authors.initials: N
authors.lastname: Tabatadze
authors.forename: Mary M
authors.initials: MM
authors.lastname: Czech
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Woolley
mesh_terms: D000818:Animals; D004958:Estradiol / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000648:ultrastructure*; D017729:Presynaptic Terminals / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022142:Secretory Vesicles / Q000648:ultrastructure*
chemical_list: D004958:Estradiol
references.citation: J Neurosci. 2010 Jun 30;30(26):8993-9006
references.pmid: 20592220
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):10035-40
references.pmid: 16788073
references.citation: Endocrinology. 2013 Feb;154(2):819-30
references.pmid: 23183182
references.citation: Neuroscience. 1996 Jul;73(2):317-34
references.pmid: 8783252
references.citation: Neurosci Lett. 1982 Nov 16;33(1):29-34
references.pmid: 6130495
references.citation: Histochem Cell Biol. 2008 Mar;129(3):243-52
references.pmid: 18197413
references.citation: Trends Neurosci. 2004 Mar;27(3):135-42
references.pmid: 15036878
references.citation: Epilepsy Behav. 2008 Jul;13(1):12-24
references.pmid: 18346939
references.citation: Mol Cell Neurosci. 2008 Oct;39(2):229-37
references.pmid: 18652899
references.citation: Acta Neurol Scand. 1976 Oct;54(4):321-47
references.pmid: 973554
references.citation: J Comp Neurol. 2003 Jun 30;461(3):333-49
references.pmid: 12746872
references.citation: J Comp Neurol. 1985 Mar 8;233(2):147-58
references.pmid: 3882777
references.citation: Neuroscience. 2006 Sep 15;141(4):2097-106
references.pmid: 16797135
references.citation: J Biol Chem. 2004 Mar 5;279(10):8602-7
references.pmid: 14681234
references.citation: Epilepsia. 2004 Jul;45(7):864-7
references.pmid: 15230714
references.citation: Neuroscience. 2005;136(1):357-69
references.pmid: 16198490
references.citation: Science. 1986 May 23;232(4753):1004-7
references.pmid: 2422758
references.citation: Hippocampus. 2011 Jun;21(6):661-77
references.pmid: 20333733
references.citation: Brain Res. 1998 Jan 19;781(1-2):351-4
references.pmid: 9507190
references.citation: Neuroscience. 1996 Jul;73(2):299-315
references.pmid: 8783251
references.citation: Brain Res. 1995 Jul 24;686(2):182-93
references.pmid: 7583284
references.citation: Mol Cell Endocrinol. 2008 May 14;286(1-2):96-103
references.pmid: 18221832
references.citation: Mol Biol Cell. 2007 Dec;18(12):4813-25
references.pmid: 17881726
references.citation: J Cell Sci. 2009 Jan 1;122(Pt 1):75-82
references.pmid: 19066284
references.citation: Neuroscience. 1991;41(1):127-35
references.pmid: 1676138
references.citation: J Neurosci. 2001 Sep 1;21(17):6532-43
references.pmid: 11517242
references.citation: Seizure. 2008 Mar;17(2):151-9
references.pmid: 18164632
references.citation: J Neurosci. 2003 Jun 1;23(11):4479-90
references.pmid: 12805288
references.citation: Neuron. 1991 Apr;6(4):517-24
references.pmid: 2015091
references.citation: J Neurosci. 2009 Feb 4;29(5):1457-68
references.pmid: 19193892
references.citation: BMC Neurosci. 2010 Mar 04;11:32
references.pmid: 20202202
references.citation: J Neurosci. 2007 Feb 21;27(8):2102-11
references.pmid: 17314305
references.citation: J Neurochem. 2000 Jun;74(6):2497-503
references.pmid: 10820211
references.citation: Hippocampus. 1992 Apr;2(2):107-25
references.pmid: 1308177
references.citation: Neuroscience. 2006;138(3):837-44
references.pmid: 16310960
references.citation: Synapse. 1995 Mar;19(3):160-9
references.pmid: 7784956
references.citation: J Microsc. 2001 Jun;202(Pt 3):468-72
references.pmid: 11422668
references.citation: FASEB J. 1994 Jun;8(9):630-8
references.pmid: 8005390
references.citation: Hippocampus. 1994 Apr;4(2):157-66
references.pmid: 7951690
references.citation: Neuron. 2001 Jan;29(1):131-43
references.pmid: 11182086
references.citation: Cell Tissue Res. 2006 Nov;326(2):583-98
references.pmid: 16847638
references.citation: J Neurosci. 2005 Jan 26;25(4):971-6
references.pmid: 15673678