title: Hippocampal neurogenesis is not enhanced by lifelong reduction of glucocorticoid levels.
abstract: Neurogenesis of dentate gyrus granule cells is generally considered to be negatively regulated by glucocorticoids. We tested the hypothesis that exposure to low plasma corticosteroid levels starting in the early postnatal period enhances granule cell proliferation rate during adulthood. Rat pups were adrenalectomized (ADX) on postnatal day 10 and were then "clamped" throughout life at low corticosterone levels via oral supplementation. Neurogenesis was determined using BrdU immunochemistry at 3 and 12 months in clamped rats as compared with age-matched, sham-operated controls. Rate of neurogenesis did not differ between the groups at either 3 or 12 months. It was significantly lower in 12-month-old compared with 3-month-old rats, despite the presence of an age-dependent increase of plasma corticosterone only in the sham-ADX rats. Granule cell layer volume, granule cell density, and granule cell degeneration (determined using apoptotic markers) were indistinguishable in the two groups, further supporting the comparable rate of neurogenesis under differing chronic glucocorticoid levels. In addition, whereas acute deprivation of plasma glucocorticoids (adrenalectomy) in adult rats evoked a burst of granule cell neurogenesis, complete elimination of these hormones (by stopping hormone supplementation) in adult, early-life ADX/clamped rats did not. These data do not support a simple inverse relationship between chronic plasma glucocorticoid levels and granule cell neurogenesis. Specifically, chronic modulation of glucocorticoid levels commencing early in life evokes additional, adaptive, and compensatory mechanisms that contribute to the regulation of granule cell proliferation.
authors.affiliation: Departments of Anatomy/Neurobiology and Pediatrics, University of California at Irvine, Irvine, CA 92697-4475, USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Brunson
authors.forename: Tallie Z
authors.initials: TZ
authors.lastname: Baram
authors.forename: Roland A
authors.initials: RA
authors.lastname: Bender
mesh_terms: D000315:Adrenalectomy; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D018161:Receptors, Mineralocorticoid; D001973:Bromodeoxyuridine
references.citation: Nature. 2001 Mar 15;410(6826):372-6
references.pmid: 11268214
references.citation: J Neurosci. 1992 Sep;12(9):3642-50
references.pmid: 1527603
references.citation: Biol Psychiatry. 1999 Dec 1;46(11):1472-9
references.pmid: 10599477
references.citation: J Neurosci. 1999 May 15;19(10):3982-91
references.pmid: 10234028
references.citation: Neuroscience. 2001;107(4):603-13
references.pmid: 11720784
references.citation: Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8856-61
references.pmid: 11447269
references.citation: Nat Neurosci. 1999 Oct;2(10):894-7
references.pmid: 10491610
references.citation: EMBO Rep. 2000 Nov;1(5):447-51
references.pmid: 11258486
references.citation: Endocrinology. 1994 Dec;135(6):2364-8
references.pmid: 7988418
references.citation: Aging (Milano). 1992 Sep;4(3):197-210
references.pmid: 1420403
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11032-7
references.pmid: 11005874
references.citation: J Comp Neurol. 1993 Apr 15;330(3):324-36
references.pmid: 8468409
references.citation: J Neurosci. 2002 Feb 1;22(3):614-8
references.pmid: 11826088
references.citation: Eur J Neurosci. 2003 Dec;18(11):3105-11
references.pmid: 14656306
references.citation: J Neurosci Methods. 1999 Nov 15;93(2):149-62
references.pmid: 10634500
references.citation: Neurobiol Aging. 2004 Mar;25(3):361-75
references.pmid: 15123342
references.citation: Horm Metab Res. 1999 Feb-Mar;31(2-3):120-5
references.pmid: 10226791
references.citation: J Neurosci. 2003 Jul 30;23(17):6826-36
references.pmid: 12890777
references.citation: Eur J Neurosci. 1998 Sep;10(9):2994-3006
references.pmid: 9758169
references.citation: J Comp Neurol. 2000 Oct 2;425(4):479-94
references.pmid: 10975875
references.citation: J Neurosci. 2000 Apr 15;20(8):2896-903
references.pmid: 10751442
references.citation: Brain Res. 1993 May 21;611(2):342-6
references.pmid: 8392896
references.citation: Endocrinology. 1998 Jul;139(7):3165-77
references.pmid: 9645690
references.citation: Endocrinology. 2004 Feb;145(2):529-40
references.pmid: 14563696
references.citation: J Comp Neurol. 1965 Jun;124(3):319-35
references.pmid: 5861717
references.citation: J Steroid Biochem Mol Biol. 1990 Nov 20;37(3):387-94
references.pmid: 2257242
references.citation: Eur J Neurosci. 2003 Jul;18(1):215-9
references.pmid: 12859354
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3168-71
references.pmid: 9501234
references.citation: Endocrinology. 1991 Mar;128(3):1385-95
references.pmid: 1847856
references.citation: Endocrinology. 2002 Nov;143(11):4184-95
references.pmid: 12399411
references.citation: Eur J Neurosci. 2001 Feb;13(4):679-86
references.pmid: 11207803
references.citation: Brain Res Dev Brain Res. 2002 Mar 31;134(1-2):77-85
references.pmid: 11947938
references.citation: Endocrinology. 1985 Dec;117(6):2505-11
references.pmid: 2998738
references.citation: Neurobiol Aging. 1992 Jan-Feb;13(1):171-4
references.pmid: 1542376
references.citation: Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13427-31
references.pmid: 10557337
references.citation: Development. 2003 Jan;130(2):391-9
references.pmid: 12466205
references.citation: J Comp Neurol. 2003 Apr 28;459(2):201-7
references.pmid: 12640670
references.citation: J Comp Neurol. 1991 Nov 15;313(3):486-93
references.pmid: 1770172
references.citation: J Comp Neurol. 1975 Jan 15;159(2):149-75
references.pmid: 1112911
references.citation: Neuroendocrinology. 2002 Dec;76(6):366-72
references.pmid: 12566944
references.citation: J Neurosci. 1996 Mar 15;16(6):2027-33
references.pmid: 8604047
references.citation: Neuroscience. 1994 Jul;61(2):203-9
references.pmid: 7969902
references.citation: Brain Res Brain Res Rev. 2001 Nov;37(1-3):273-86
references.pmid: 11744092
references.citation: Science. 1997 Sep 12;277(5332):1659-62
references.pmid: 9287218
references.citation: Prog Brain Res. 1988;73:101-20
references.pmid: 3047791
references.citation: Ann Neurol. 2001 Mar;49(3):304-12
references.pmid: 11261504
references.citation: Neuroendocrinology. 2003 Jan;77(1):24-31
references.pmid: 12624538
references.citation: Endocrinology. 1990 Aug;127(2):832-42
references.pmid: 2164922
references.citation: Endocrinology. 1997 Aug;138(8):3249-58
references.pmid: 9231775
references.citation: Neuroscience. 1980;5(11):2003-12
references.pmid: 7432634
references.citation: Mol Endocrinol. 1989 Nov;3(11):1886-94
references.pmid: 2558306
references.citation: Science. 1982 May 21;216(4548):890-2
references.pmid: 7079742
references.citation: J Neurosci. 2001 Mar 1;21(5):1628-34
references.pmid: 11222653
references.citation: Prog Brain Res. 1970;32:79-85
references.pmid: 4322026
references.citation: Nat Med. 1998 Nov;4(11):1313-7
references.pmid: 9809557
references.citation: Nature. 2002 Feb 28;415(6875):1030-4
references.pmid: 11875571
references.citation: Neuroreport. 1995 Dec 15;6(18):2479-82
references.pmid: 8741746
references.citation: Brain Res. 1991 Jul 19;554(1-2):312-5
references.pmid: 1933312
references.citation: J Neurosci. 1998 May 1;18(9):3206-12
references.pmid: 9547229
references.citation: Stress. 1998 Jul;2(3):159-69
references.pmid: 9787264
references.citation: Brain Res. 1990 Apr 23;514(1):37-48
references.pmid: 2357528
references.citation: J Comp Neurol. 2001 Jul 9;435(4):406-17
references.pmid: 11406822
references.citation: J Neurosci. 1998 Sep 15;18(18):7462-73
references.pmid: 9736665
references.citation: Neuroscience. 1999 Jan;88(1):269-79
references.pmid: 10051206
references.citation: Recent Prog Horm Res. 1987;43:113-73
references.pmid: 2819993
references.citation: Cell Mol Neurobiol. 1993 Aug;13(4):349-72
references.pmid: 8252607
references.citation: Brain Res Dev Brain Res. 1999 May 14;114(2):265-8
references.pmid: 10320766
references.citation: Proc Natl Acad Sci U S A. 1999 May 11;96(10):5768-73
references.pmid: 10318959
references.citation: Stress. 1996 Jul;1(1):51-64
references.pmid: 9807061
references.citation: Endocrinology. 2001 Jan;142(1):89-97
references.pmid: 11145570
references.citation: J Cell Biochem. 2003 Jan 1;88(1):41-50
references.pmid: 12461773
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14385-90
references.pmid: 14614143