Object recognition memory and BDNF expression are reduced in young TgCRND8 mice.
The TgCRND8 mouse model of Alzheimer's disease exhibits progressive cortical and hippocampal β-amyloid accumulation, resulting in plaque pathology and spatial memory impairment by 3 months of age. We tested whether TgCRND8 cognitive function is disrupted prior to the appearance of macroscopic plaques in an object recognition task. We found profound deficits in 8-week-old mice. Animals this age were not impaired on the Morris water maze task. TgCRND8 and littermate controls did not differ in their duration of object exploration or optokinetic responses. Thus, visual and motor dysfunction did not confound the phenotype. Object memory deficits point to the frontal cortex and hippocampus as early targets of functional disruption. Indeed, we observed altered levels of brain-derived neurotrophic factor (BDNF) messenger ribonucleic acid (mRNA) in these brain regions of preplaque TgCRND8 mice. Our findings suggest that object recognition provides an early index of cognitive impairment associated with amyloid exposure and reduced brain-derived neurotrophic factor expression in the TgCRND8 mouse.
Francis
Beverly M
BM
Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Kim
John
J
Barakat
Meredith E
ME
Fraenkl
Stephan
S
Yücel
Yeni H
YH
Peng
Shiyong
S
Michalski
Bernadeta
B
Fahnestock
Margaret
M
McLaurin
Joanne
J
Mount
Howard T J
HT
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D006224:Cricetinae; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics*; D005625:Frontal Lobe / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D008647:Mesocricetus; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D021641:Recognition, Psychology / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger
Neuroreport. 1997 Mar 24;8(5):1173-8
9175108
Behav Brain Res. 2005 May 28;160(2):344-55
15863231
Proc Natl Acad Sci U S A. 2004 Oct 5;101(40):14515-20
15452348
Science. 2002 Jul 19;297(5580):353-6
12130773
J Neurochem. 2007 Oct;103(1):216-28
17587310
EMBO J. 1990 Aug;9(8):2459-64
2369898
J Neurosci. 2004 Jul 28;24(30):6799-809
15282285
Neurobiol Aging. 1992 Jan-Feb;13(1):179-89
1311804
J Neurosci. 2009 Jul 22;29(29):9321-9
19625522
Neurobiol Aging. 2006 Jul;27(7):955-64
15993515
Sci Aging Knowledge Environ. 2006 Mar 08;2006(6):re1
16525193
Neurobiol Aging. 2006 Feb;27(2):270-7
16399212
J Neurosci. 2002 Mar 1;22(5):1858-67
11880515
Ann Neurol. 1991 Oct;30(4):572-80
1789684
Nature. 2000 Dec 21-28;408(6815):979-82
11140685
J Neurochem. 2005 Jun;93(6):1412-21
15935057
Prog Neurobiol. 1998 Feb;54(3):313-32
9481801
Vision Res. 1990;30(4):549-55
2339509
Nat Med. 2009 Mar;15(3):331-7
19198615
Acta Neuropathol. 1991;82(4):239-59
1759558
J Neurosci Methods. 2004 Sep 30;138(1-2):7-13
15325106
J Biol Chem. 2001 May 18;276(20):17301-6
11278679
Neuropsychologia. 2005;43(1):60-8
15488906
Neurobiol Dis. 2009 Sep;35(3):426-32
19524672
Neurobiol Dis. 2006 Aug;23(2):260-72
16766197
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6826-31
10841577
Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4611-6
15557474
Exp Brain Res. 1983;50(2-3):433-41
6605872
J Neurosci. 2004 Mar 10;24(10):2421-30
15014117
J Neurosci. 2007 Mar 7;27(10):2628-35
17344400
J Neurosci. 2004 Apr 14;24(15):3826-36
15084664
Neurosci Biobehav Rev. 2007;31(5):673-704
17368764
Mol Psychiatry. 2007 Jul;12(7):656-70
17264839
J Neurosci Methods. 2008 Mar 15;168(2):422-30
18096240
Behav Brain Res. 2003 Dec 17;147(1-2):49-54
14659569
Learn Mem. 2002 Mar-Apr;9(2):58-65
11992016
Behav Brain Res. 2006 Jun 3;170(1):99-109
16540184
Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):648-52
1731336
Exp Neurol. 2002 Jun;175(2):398-406
12061869
Neurobiol Aging. 2004 Jul;25(6):713-8; discussion 743-6
15165692
Neuroscience. 2007 Jun 15;147(1):28-36
17499931
J Neurosci. 2004 Jun 30;24(26):5901-8
15229237
Genes Brain Behav. 2009 Oct;8(7):676-84
19531156
J Biol Chem. 2001 Jun 15;276(24):21562-70
11279122
Neurobiol Learn Mem. 2004 Jul;82(1):26-34
15183168
Neuroscience. 1997 May;78(2):431-48
9145800
Neurobiol Dis. 2007 Sep;27(3):328-38
17656099
Behav Brain Res. 1988 Nov 1;31(1):47-59
3228475
Neuroimage. 2003 Feb;18(2):525-41
12595205
J Pharmacol Exp Ther. 2002 Apr;301(1):187-96
11907173
Neuroreport. 2008 Jun 11;19(9):965-8
18521002
J Neural Transm (Vienna). 2006 Sep;113(9):1217-24
16362629
Genes Brain Behav. 2002 Aug;1(3):142-55
12884970
Behav Neurosci. 1994 Feb;108(1):11-8
8192836
Eur J Neurosci. 2003 Jan;17(2):388-96
12542676
Exp Neurol. 2008 Mar;210(1):164-71
18053988
Exp Aging Res. 2008 Jul-Sep;34(3):267-81
18568983
Eur J Neurosci. 2004 Dec;20(11):3157-64
15579170