title: Evidence for reduced experience-dependent dendritic spine plasticity in the aging prefrontal cortex.
abstract: Cognitive functions that require the prefrontal cortex are highly sensitive to aging in humans, nonhuman primates, and rodents, although the neurobiological correlates of this vulnerability remain largely unknown. It has been proposed that dendritic spines represent the primary site of structural plasticity in the adult brain, and recent data have supported the hypothesis that aging is associated with alterations of dendritic spine morphology and plasticity in prefrontal cortex. However, no study to date has directly examined whether aging alters the capacity for experience-dependent spine plasticity in aging prefrontal neurons. To address this possibility, we used young, middle-aged, and aged rats in a behavioral stress paradigm known to produce spine remodeling in prefrontal cortical neurons. In young rats, stress resulted in dendritic spine loss and altered patterns of spine morphology; in contrast, spines from middle-aged and aged animals were remarkably stable and did not show evidence of remodeling. The loss of stress-induced spine plasticity observed in aging rats occurred alongside robust age-related reductions in spine density and shifts in remaining spine morphology. Together, the data presented here provide the first evidence that experience-dependent spine plasticity is altered by aging in prefrontal cortex, and support a model in which dendritic spines become progressively less plastic in the aging brain.
authors: Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Erik B
authors: EB
authors: Bloss
authors: William G
authors: WG
authors: Janssen
authors: Daniel T
authors: DT
authors: Ohm
authors: Frank J
authors: FJ
authors: Yuk
authors: Shannon
authors: S
authors: Wadsworth
authors: Karl M
authors: KM
authors: Saardi
authors: Bruce S
authors: BS
authors: McEwen
authors: John H
authors: JH
authors: Morrison
references: Eur J Neurosci. 2001 Nov;14(10):1739-51
references: 11860468
references: J Neurosci. 2010 May 12;30(19):6726-31
references: 20463234
references: J Neurosci. 2004 Sep 1;24(35):7648-53
references: 15342731
references: Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17957-62
references: 19805148
references: Nat Rev Neurosci. 2009 Sep;10(9):647-58
references: 19693029
references: Nat Neurosci. 1999 Jul;2(7):618-24
references: 10409387
references: J Comp Neurol. 2008 Mar 1;507(1):1141-50
references: 18157834
references: Nat Rev Neurosci. 2009 Jun;10(6):434-45
references: 19401723
references: Exp Neurol. 2005 Nov;196(1):199-203
references: 16095592
references: Neuron. 2004 Dec 2;44(5):749-57
references: 15572107
references: Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):359-64
references: 18172209
references: Neurosci Biobehav Rev. 2010 Sep;35(1):2-16
references: 19822172
references: Exp Gerontol. 1999 Sep;34(6):721-32
references: 10579633
references: Neuroscience. 2000;97(2):253-66
references: 10799757
references: Am J Anat. 1970 Apr;127(4):321-55
references: 4985058
references: Nat Rev Neurosci. 2006 Jan;7(1):30-40
references: 16371948
references: Nature. 2002 Dec 19-26;420(6917):812-6
references: 12490949
references: Proc Natl Acad Sci U S A. 1986 May;83(9):3027-31
references: 3458260
references: J Neurosci. 1989 Aug;9(8):2982-97
references: 2769375
references: Neurobiol Aging. 2009 Apr;30(4):507-14
references: 19231028
references: J Neurosci. 2008 Dec 10;28(50):13592-608
references: 19074033
references: PLoS One. 2008 Apr 23;3(4):e1997
references: 18431482
references: Neurobiol Aging. 2009 May;30(5):782-92
references: 17919783
references: Annu Rev Physiol. 2009;71:261-82
references: 19575680
references: J Neurosci. 1990 Oct;10(10):3247-54
references: 2170594
references: Neurobiol Aging. 2004 Mar;25(3):407-16
references: 15123345
references: Nature. 2004 Jun 17;429(6993):761-6
references: 15190253
references: Ann N Y Acad Sci. 2008 Mar;1124:127-44
references: 18400928
references: Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11465-70
references: 17592140
references: Science. 2009 Jul 31;325(5940):621-5
references: 19644122
references: Trends Neurosci. 2003 Jul;26(7):360-8
references: 12850432
references: Cereb Cortex. 2006 Mar;16(3):313-20
references: 15901656
references: Neuroendocrinology. 1984 Jan;38(1):33-8
references: 6537997
references: Nat Neurosci. 2001 Nov;4(11):1086-92
references: 11687814
references: Cereb Cortex. 2009 Oct;19(10):2479-84
references: 19193712
references: Nature. 2002 Dec 19-26;420(6917):788-94
references: 12490942
references: Trends Neurosci. 2004 Oct;27(10):607-13
references: 15374672
references: Annu Rev Psychol. 1997;48:339-70
references: 9046563
references: J Comp Neurol. 1997 Oct 6;386(4):661-80
references: 9378859
references: Neuroscience. 2009 Dec 1;164(2):798-808
references: 19723561
references: Nat Neurosci. 2004 Oct;7(10):1104-12
references: 15361876
references: Cereb Cortex. 2003 Sep;13(9):950-61
references: 12902394
references: Neurobiol Aging. 2012 Feb;33(2):421.e17-28
references: 21030115
references: J Neurosci. 2010 Jun 2;30(22):7507-15
references: 20519525
references: Nat Protoc. 2006;1(4):2152-61
references: 17487207
references: Nature. 2009 Dec 17;462(7275):920-4
references: 19946265
references: Nature. 2006 Jun 22;441(7096):979-83
references: 16791195
references: J Neurosci. 2000 Sep 15;20(18):RC95
references: 10974092
references: Nat Neurosci. 1998 May;1(1):69-73
references: 10195112
references: Nat Rev Neurosci. 2000 Oct;1(1):59-65
references: 11252769
references: Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):912-7
references: 19139412
references: Neuron. 2005 Jan 20;45(2):279-91
references: 15664179
references: Neurobiol Aging. 2009 Apr;30(4):646-55
references: 17889407
references: Neurobiol Aging. 2006 Oct;27(10):1484-93
references: 16183172
references: Endocr Rev. 1986 Aug;7(3):284-301
references: 3527687