title: Astrocytes from acyclic female rats exhibit lowered capacity for neuronal differentiation.
abstract: Astrocytes comprise a large proportion of the central nervous system support cells and play a critical role in neural injury and repair. The present study examined the impact of ovarian aging using an ex vivo model system, where astrocytes were derived from the olfactory bulb of young, reproductively competent females and reproductive senescent females. Cellular morphology and the spatial pattern of laminin deposition was altered in astrocyte cultures derived from reproductive senescent females. Young adult astrocytes had a flattened polygonal shape with actin bundles at the cell edges, while reproductive senescent astrocytes had a contractile appearance with thick stress fibers visible throughout the cell. Moreover, in reproductive senescent astrocytes, BDNF was elevated with a concomitant reduction in expression of the BDNF receptor, TrkB. To examine the ability of astrocytes derived from young adult and reproductive senescent females to promote neuronal differentiation, neural progenitor cells (NPCs) were co-cultured with astrocytes derived from these groups. At day 4 in vitro, MAP-2(+) NPCs were located in smaller clusters when co-cultured with young adult astrocytes and in large clusters when co-cultured with older astrocytes. At days 6 and 10, neuronal differentiation was significantly reduced in reproductive senescent astrocyte-NPC co-cultures, as determined by NeuN(+) cell numbers and MAP-2(+) process lengths. Furthermore, estrogen only enhanced neuronal differentiation in young adult-NPC co-cultures. The ovarian age-related astrocyte phenotype thus limits the ability of this cell to promote neuronal differentiation in NPC populations and suggests that the astrocyte-mediated microenvironment in older acyclic females is less conducive to repair following neurovascular injury.
authors.affiliation: TAMU Health Science Center, Department of Neuroscience and Experimental Therapeutics, College Station, TX 77843-1114, USA.
authors.forename: Danielle K
authors.initials: DK
authors.lastname: Lewis
authors.forename: Heather R
authors.initials: HR
authors.lastname: Woodin
authors.forename: Farida
authors.initials: F
authors.lastname: Sohrabji
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
references.citation: J Clin Invest. 1999 Jun;103(11):1561-70
references.pmid: 10359565
references.citation: Neuroreport. 2001 Aug 28;12(12):2673-7
references.pmid: 11522946
references.citation: FEBS Lett. 1987 Oct 19;223(1):117-21
references.pmid: 3666133
references.citation: Dev Biol. 1988 Dec;130(2):774-85
references.pmid: 3143614
references.citation: J Biol Chem. 1994 Feb 4;269(5):3739-44
references.pmid: 8106419
references.citation: J Immunol. 1987 Oct 15;139(8):2593-7
references.pmid: 3116087
references.citation: EMBO J. 1984 Mar;3(3):683-6
references.pmid: 6370690
references.citation: J Neurosci. 2006 Dec 13;26(50):13007-16
references.pmid: 17167090
references.citation: J Neuroimmunol. 2008 Mar;195(1-2):47-59
references.pmid: 18328572
references.citation: Brain Res Mol Brain Res. 2000 Dec 28;85(1-2):77-84
references.pmid: 11146109
references.citation: J Neurotrauma. 2004 Apr;21(4):415-27
references.pmid: 15115591
references.citation: Endocrinology. 2004 Dec;145(12):5471-5
references.pmid: 15471968
references.citation: J Neurosci. 2002 Sep 15;22(18):8034-41
references.pmid: 12223557
references.citation: Nature. 1987 Jan 15-21;325(6101):253-7
references.pmid: 3543687
references.citation: Ann N Y Acad Sci. 2005 Jun;1052:75-90
references.pmid: 16024752
references.citation: Exp Neurol. 1997 Sep;147(1):1-9
references.pmid: 9294397
references.citation: Science. 1988 Nov 4;242(4879):692-9
references.pmid: 3055291
references.citation: J Neurosci. 1998 Oct 1;18(19):7768-78
references.pmid: 9742147
references.citation: J Neurosci. 1992 Nov;12(11):4565-74
references.pmid: 1432110
references.citation: Science. 2001 Jan 26;291(5504):657-61
references.pmid: 11158678
references.citation: Proc Natl Acad Sci U S A. 1980 Nov;77(11):6624-8
references.pmid: 6256751
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4710-5
references.pmid: 11296300
references.citation: Cell Tissue Res. 1997 Nov;290(2):385-93
references.pmid: 9321702
references.citation: Folia Biol (Praha). 2006;52(5):149-55
references.pmid: 17116286
references.citation: J Neurobiol. 1998 Jun 15;35(4):395-425
references.pmid: 9624622
references.citation: Science. 1992 Mar 27;255(5052):1707-10
references.pmid: 1553558
references.citation: Circ Res. 2004 May 28;94(10):1383-91
references.pmid: 15087418
references.citation: Nature. 2000 Jun 22;405(6789):951-5
references.pmid: 10879536
references.citation: Neurobiol Aging. 2001 Mar-Apr;22(2):309-19
references.pmid: 11182481
references.citation: J Neuroendocrinol. 2002 Nov;14(11):904-10
references.pmid: 12421344
references.citation: Environ Health Perspect. 1989 Mar;80:127-42
references.pmid: 2647474
references.citation: J Immunol. 1982 Dec;129(6):2413-9
references.pmid: 6982921
references.citation: Neuroscience. 1993 Mar;53(2):395-401
references.pmid: 8492911
references.citation: Dev Biol. 1989 Jun;133(2):489-501
references.pmid: 2525104
references.citation: Eur J Neurosci. 2007 Oct;26(7):1780-90
references.pmid: 17883412
references.citation: Neurobiol Aging. 2005 May;26(5):705-15
references.pmid: 15708446
references.citation: Neuroscience. 1997 Sep;80(2):427-36
references.pmid: 9284346
references.citation: Neurobiol Aging. 2003 Sep;24(5):733-43
references.pmid: 12885581
references.citation: Cell Mol Neurobiol. 1990 Sep;10(3):447-57
references.pmid: 2174743
references.citation: J Neurosci Res. 2004 Apr 1;76(1):76-85
references.pmid: 15048931
references.citation: J Cell Biol. 1983 Jan;96(1):76-83
references.pmid: 6186675
references.citation: J Biochem Mol Biol. 2006 Jul 31;39(4):339-45
references.pmid: 16889675
references.citation: Neuron. 1993 Nov;11(5):951-66
references.pmid: 8240816
references.citation: Brain Res Mol Brain Res. 2005 Jul 29;138(1):1-7
references.pmid: 15896872
references.citation: J Neurosci Res. 2006 Dec;84(8):1656-68
references.pmid: 17061253
references.citation: BMC Neurosci. 2005 Sep 13;6:59
references.pmid: 16159388
references.citation: J Neurosci. 1991 Feb;11(2):318-26
references.pmid: 1992003
references.citation: J Comp Neurol. 2007 Feb 20;500(6):1064-75
references.pmid: 17183542
references.citation: J Mol Histol. 2004 Nov;35(8-9):771-83
references.pmid: 15609090
references.citation: Dev Biol. 2006 Nov 15;299(2):455-65
references.pmid: 17005175
references.citation: J Neurobiol. 2000 Nov 5;45(2):61-74
references.pmid: 11018768
references.citation: J Neurosci. 2005 Apr 6;25(14):3638-50
references.pmid: 15814795
references.citation: Pharmacol Ther. 1995 Jan;65(1):1-18
references.pmid: 7716180
references.citation: Brain Res. 1996 Dec 16;743(1-2):56-62
references.pmid: 9017230
references.citation: J Neurosci. 1999 May 1;19(9):3287-97
references.pmid: 10212288
references.citation: Science. 1997 Sep 12;277(5332):1684-7
references.pmid: 9287225
references.citation: Alcohol Clin Exp Res. 2007 Feb;31(2):324-35
references.pmid: 17250626
references.citation: Keio J Med. 1997 Jun;46(2):55-60
references.pmid: 9212587
references.citation: Alcohol Clin Exp Res. 2007 Apr;31(4):694-703
references.pmid: 17374049
references.citation: Neurobiol Dis. 2005 Nov;20(2):461-70
references.pmid: 15893467
references.citation: Neuroscience. 2001;105(1):33-41
references.pmid: 11483298
references.citation: Neuroscience. 2006;138(1):47-53
references.pmid: 16388909
references.citation: Int J Dev Neurosci. 2000 Feb;18(1):101-11
references.pmid: 10708911
references.citation: Brain Res. 2004 Dec 24;1030(1):116-24
references.pmid: 15567343
references.citation: Brain Res. 1987 Jul;431(1):87-97
references.pmid: 3620987