Temporal gene expression profile in hippocampus of mice treated with D-galactose.
(1) Rodent chronically treated with D-galactose (D-gal) is increasingly used in pharmacological studies on aging; however, its mechanism remains unclear. The present study investigated the alterations of gene expression in the hippocampus of D-gal-treated mice. (2) C57 mice were subcutaneously injected with D-gal for 2, 4, and 8 weeks or vehicle, and then were subjected to behavioral tests. Gene expression profiles in hippocampus of each group were finally examined with cDNA microarray. (3) Both 4- and 8-week D-gal treatment led to a decrease of discrimination index in object recognition test, and 8-week D-gal-treated mice showed significant spatial learning & memory impairment in Morris water maze test. In comparison with the vehicle control group, the 2-, 4-, and 8-week D-gal treatment repressed the expression of 10, 13, and 30 genes by 2-fold or more, respectively. The early pattern was mainly characterized by down regulation of genes involved in ion transport. The delayed pattern included genes involved in protein biosynthesis, transport and signal transduction, which were highly related to synaptic functions. (4) These findings will contribute to the understanding of the mechanism of learning and memory impairment in mice treated with D-galactose.
Wei
Haifeng
H
Department of Pharmacology, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Xuan-wu Hospital of Capital Medical University, 45 Chang-chun Street, Xuan-wu District, Beijing, China.
Cai
Yanning
Y
Chu
Jin
J
Li
Chunyang
C
Li
Lin
L
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004334:Drug Administration Schedule; D005690:Galactose / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D017136:Ion Transport / Q000187:drug effects / Q000235:genetics; D007859:Learning Disabilities / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D005690:Galactose
Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9701-5
10920207
J Cancer Res Clin Oncol. 2002 Jul;128(7):369-79
12136251
Neurochem Int. 2002 Dec;41(6):383-9
12213225
J Clin Invest. 1960 Jan;39:178-84
14432120
J Neurosci. 1988 Jul;8(7):2640-51
3074159
Am J Physiol Renal Physiol. 2001 Oct;281(4):F674-8
11553514
J Neurochem. 2002 Sep;82(5):1221-8
12358769
J Mol Neurosci. 1997 Dec;9(3):151-66
9481617
Mol Genet Metab. 2005 Nov;86(3):360-71
16169270
J Neurochem. 1995 Jan;64(1):340-53
7798931
Hippocampus. 2000;10(4):431-7
10985282
Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9654-9
9275178
J Biopharm Stat. 2003 Feb;13(1):57-74
12635903
Science. 1979 Sep 28;205(4413):1395-7
472754
J Pediatr. 1975 Jul;87(1):50-57
1151546
J Ocul Pharmacol Ther. 1997 Dec;13(6):537-50
9436157
J Neurosci. 2000 Aug 15;20(16):5924-31
10934239
Science. 2005 Feb 25;307(5713):1282-8
15731448
J Neurophysiol. 1994 Sep;72(3):1438-42
7807226
J Clin Endocrinol Metab. 1996 Apr;81(4):1329-31
8636327
Neurochem Res. 1994 Mar;19(3):321-30
8177372
J Neurophysiol. 1998 Sep;80(3):1567-70
9744962
Brain Res. 1991 Feb 1;540(1-2):237-42
2054616
Behav Brain Res. 2005 Feb 28;157(2):245-51
15639175
Eur J Neurosci. 2003 Sep;18(5):1279-85
12956726
Exp Mol Med. 2001 Dec 31;33(4):220-5
11795483
Learn Mem. 2002 Jul-Aug;9(4):202-13
12177233
Gerontology. 2002 Sep-Oct;48(5):279-81
12169791
Biogerontology. 2003;4(1):15-8
12652185
Yao Xue Xue Bao. 2002 Jan;37(1):1-4
12579889
Science. 2001 Mar 23;291(5512):2417-9
11264539
Acta Pharmacol Sin. 2001 Dec;22(12):1078-83
11749803
Neurosci Behav Physiol. 1997 Jan-Feb;27(1):49-52
9109115
Indian J Biochem Biophys. 1998 Dec;35(6):364-71
10412231
Cell Struct Funct. 2003 Oct;28(5):419-29
14745134
Mech Ageing Dev. 1999 May 17;108(3):239-51
10405984
Brain Res Dev Brain Res. 2001 Jul 23;129(1):81-93
11454415
Brain Res. 1990 Jan 1;506(1):46-52
2154278
Anal Biochem. 1987 Apr;162(1):156-9
2440339