title: Age-related alterations in the expression of genes and synaptic plasticity associated with nitric oxide signaling in the mouse dorsal striatum.
abstract: Age-related alterations in the expression of genes and corticostriatal synaptic plasticity were studied in the dorsal striatum of mice of four age groups from young (2-3 months old) to old (18-24 months of age) animals. A significant decrease in transcripts encoding neuronal nitric oxide (NO) synthase and receptors involved in its activation (NR1 subunit of the glutamate NMDA receptor and D1 dopamine receptor) was found in the striatum of old mice using gene array and real-time RT-PCR analysis. The old striatum showed also a significantly higher number of GFAP-expressing astrocytes and an increased expression of astroglial, inflammatory, and oxidative stress markers. Field potential recordings from striatal slices revealed age-related alterations in the magnitude and dynamics of electrically induced long-term depression (LTD) and significant enhancement of electrically induced long-term potentiation in the middle-aged striatum (6-7 and 12-13 months of age). Corticostriatal NO-dependent LTD induced by pharmacological activation of group I metabotropic glutamate receptors underwent significant reduction with aging and could be restored by inhibition of cGMP hydrolysis indicating that its age-related deficit is caused by an altered NO-cGMP signaling cascade. It is suggested that age-related alterations in corticostriatal synaptic plasticity may result from functional alterations in receptor-activated signaling cascades associated with increasing neuroinflammation and a prooxidant state.
authors.affiliation: Department of Molecular Neurophysiology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany.
authors.forename: Aisa N
authors.initials: AN
authors.lastname: Chepkova
authors.affiliation: Department of Molecular Neurophysiology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schönfeld
authors.affiliation: Department of Molecular Neurophysiology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Sergeeva
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017072:Neostriatum / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D005904:Glial Fibrillary Acidic Protein; C409466:NR1 NMDA receptor; D009419:Nerve Tissue Proteins; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; C098593:dopamine D1A receptor; C528900:glial fibrillary astrocytic protein, mouse; D049452:Green Fluorescent Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
references.citation: Circ Res. 2005 Apr 29;96(8):818-22
references.pmid: 15860762
references.citation: Neuropharmacology. 2010 Mar;58(3):624-31
references.pmid: 19969007
references.citation: Neuroscience. 1996 Aug;73(3):733-50
references.pmid: 8809794
references.citation: Synapse. 2006 Sep 1;60(3):223-38
references.pmid: 16739119
references.citation: PLoS One. 2014;9(2):e90279
references.pmid: 24587312
references.citation: Nat Neurosci. 2002 May;5(5):446-51
references.pmid: 11976704
references.citation: Neuroimage. 2011 Mar 1;55(1):194-203
references.pmid: 21167945
references.citation: Neurosci Biobehav Rev. 2015 Feb;49:135-56
references.pmid: 25511817
references.citation: Brain Res. 2005 Jun 21;1047(2):148-58
references.pmid: 15901483
references.citation: Front Syst Neurosci. 2011 Jun 30;5:55
references.pmid: 21747761
references.citation: Neurobiol Aging. 2002 Sep-Oct;23(5):795-807
references.pmid: 12392783
references.citation: Neurobiol Learn Mem. 2008 Jan;89(1):70-5
references.pmid: 17942327
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Nov 15;827(1):65-75
references.pmid: 16183338
references.citation: Neurobiol Aging. 2012 Aug;33(8):1792-9
references.pmid: 21684039
references.citation: Pol J Pharmacol. 1997 Nov-Dec;49(6):401-10
references.pmid: 9566043
references.citation: Clin Sci (Lond). 2013 Oct;125(8):361-82
references.pmid: 23767990
references.citation: J Neurochem. 2012 Aug;122(3):545-56
references.pmid: 22639911
references.citation: Brain Res Dev Brain Res. 2005 Aug 8;158(1-2):72-81
references.pmid: 16005523
references.citation: Funct Neurol. 1991 Jul-Sep;6(3):227-9
references.pmid: 1835951
references.citation: J Neurosci. 1999 Apr 1;19(7):2489-99
references.pmid: 10087063
references.citation: Nat Protoc. 2008;3(6):1101-8
references.pmid: 18546601
references.citation: Neurobiol Aging. 2010 Sep;31(9):1649-53
references.pmid: 18986737
references.citation: Front Aging Neurosci. 2010 Jan 04;1:6
references.pmid: 20552057
references.citation: Neurobiol Aging. 1987 Jan-Feb;8(1):51-4
references.pmid: 2951609
references.citation: Prog Neurobiol. 2000 Jun;61(3):231-65
references.pmid: 10727775
references.citation: Int J Dev Neurosci. 1990;8(6):689-708
references.pmid: 2288244
references.citation: Free Radic Biol Med. 2011 Oct 1;51(7):1289-301
references.pmid: 21777669
references.citation: J Physiol. 2011 Mar 15;589(Pt 6):1349-66
references.pmid: 21242252
references.citation: Synapse. 2001 Sep 15;41(4):285-93
references.pmid: 11494399
references.citation: Eur J Neurosci. 2007 Oct;26(7):1889-94
references.pmid: 17868368
references.citation: Age (Dordr). 2013 Jun;35(3):621-35
references.pmid: 22367548
references.citation: Nucleic Acids Res. 2001 May 1;29(9):e45
references.pmid: 11328886
references.citation: Curr Opin Immunol. 2004 Feb;16(1):42-7
references.pmid: 14734109
references.citation: Arch Gerontol Geriatr. 2000 Jun 1;30(3):269-279
references.pmid: 10867170
references.citation: Neurobiol Aging. 1993 May-Jun;14(3):197-206
references.pmid: 8391661
references.citation: Dev Biol. 1997 Jul 1;187(1):36-42
references.pmid: 9224672
references.citation: Pol J Pharmacol. 1993 Mar-Apr;45(2):109-31
references.pmid: 8401765
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1199-204
references.pmid: 15657149
references.citation: Neurobiol Aging. 2012 Mar;33(3):623.e1-623.e13
references.pmid: 21524432
references.citation: Brain Behav Immun. 2011 Feb;25(2):181-213
references.pmid: 20970492
references.citation: Neuron. 2008 Nov 26;60(4):543-54
references.pmid: 19038213
references.citation: Neurobiol Aging. 2012 Jan;33(1):204.e1-11
references.pmid: 20888078
references.citation: Trends Neurosci. 2004 Aug;27(8):460-7
references.pmid: 15271493
references.citation: Rev Neurosci. 2003;14(3):207-16
references.pmid: 14513864
references.citation: Neurobiol Aging. 1998 May-Jun;19(3):259-65
references.pmid: 9662001
references.citation: Neuropharmacology. 2001 Jun;40(7):839-46
references.pmid: 11378154
references.citation: J Chem Neuroanat. 1993 May-Jun;6(3):131-45
references.pmid: 8102059
references.citation: Brain Res Rev. 2008 Aug;58(2):340-53
references.pmid: 18036669
references.citation: Neurobiol Aging. 2012 Aug;33(8):1842.e1-14
references.pmid: 22300951
references.citation: J Neurosci. 2000 Nov 15;20(22):8443-51
references.pmid: 11069952
references.citation: Mov Disord. 2010 Aug 15;25(11):1568-76
references.pmid: 20623773
references.citation: J Neuroinflammation. 2006 Nov 09;3:30
references.pmid: 17094809
references.citation: J Neurosci. 2009 Sep 30;29(39):12115-24
references.pmid: 19793969
references.citation: Aging Cell. 2009 Jun;8(3):277-87
references.pmid: 19627267
references.citation: J Neurosci. 1988 Oct;8(10):3750-6
references.pmid: 2848109
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20564-9
references.pmid: 18077376
references.citation: Brain Res. 2000 Jan 31;854(1-2):239-44
references.pmid: 10784129
references.citation: Neurobiol Aging. 1994 Sep-Oct;15(5):651-5
references.pmid: 7824058
references.citation: Brain Res. 2002 Sep 27;951(1):36-42
references.pmid: 12231454
references.citation: Adv Drug Deliv Rev. 2009 Nov 30;61(14):1283-98
references.pmid: 19716388
references.citation: Brain. 2011 Feb;134(Pt 2):375-87
references.pmid: 21183486
references.citation: Curr Pharm Des. 2010;16(6):609-18
references.pmid: 20388071
references.citation: Eur J Neurosci. 2001 Mar;13(6):1071-7
references.pmid: 11285003
references.citation: Neurobiol Aging. 1993 Sep-Oct;14(5):421-9
references.pmid: 8247224
references.citation: Brain Res. 2003 Feb 21;964(1):159-63
references.pmid: 12573525
references.citation: Neurosci Res. 1996 Mar;24(4):393-402
references.pmid: 8861109
references.citation: Brain Res. 2007 Mar 2;1135(1):58-68
references.pmid: 17210145
references.citation: Free Radic Res. 2003 Aug;37(8):795-808
references.pmid: 14567438
references.citation: Neuroscience. 2012 Jul 26;215:149-59
references.pmid: 22554779
references.citation: Brain Res. 2002 Apr 12;933(1):31-41
references.pmid: 11929633
references.citation: Parkinsonism Relat Disord. 2012 Jun;18(5):426-32
references.pmid: 22176812
references.citation: Brain Res. 1993 Feb 26;604(1-2):106-11
references.pmid: 8457839
references.citation: Circ Res. 2012 May 11;110(10):1364-90
references.pmid: 22581922
references.citation: J Neurophysiol. 2002 Dec;88(6):3010-20
references.pmid: 12466426
references.citation: Annu Rev Pharmacol Toxicol. 2004;44:269-96
references.pmid: 14744247