Effects of glucocorticoids on age-related impairments of hippocampal structure and function in mice.
Effects of glucocorticoids (GCs) on maze-learning performances and hippocampal morphology were observed in male C57BL/6Cr mice. Correlations between aging, GCs and maze-learning performances were also studied. (2) Eight-arm radial maze was used in maze-learning tests. Learning performance was assessed by the parameters of time of getting all the bait, number of reentry errors into the already-entered arm with bait, and number of missed entries into an unbaited arm. Brain sections, 8 mum thick, were Nissl-stained with cresyl violet or stained immunocytochemically with antibodies against neurofilaments. (3) With aging, normal pyramidal cells decreased gradually in amount, and degenerating cells increased since the age of 18 months, accompanied with the maze-learning deficit. Here we have suggested that these changes were associated with the age-related deficits in adaptation tolerance of neurons to stress. In addition, the age-related deficits in plasticity of hippocampal neurons to GCs in young mice (3 months of age) resulted in an increase in plasma corticosterone (CORT) concentrations, degeneration of hippocampal pyramidal cells, as well as maze-learning deficits. (4) In conclusion, our data indicated that CORT caused the degeneration of hippocampal pyramidal cells and the impairment of memory.
He
Wen-Bin
WB
Department of Pharmacology, Institute of Materia Medica, Key Laboratory of Bioactive Substances and Resources Utilization, Ministry of Education, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
Zhang
Jun-Long
JL
Hu
Jin-Feng
JF
Zhang
Yun
Y
Machida
Takeo
T
Chen
Nai-Hong
NH
D000375:Aging / Q000473:pathology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology; D005938:Glucocorticoids / Q000097:blood / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D003345:Corticosterone
J Anat. 2000 Nov;197 Pt 4:553-62
11197528
Neurobiol Aging. 2004 Mar;25(3):407-16
15123345
Science. 1978 Dec 8;202(4372):1098-102
715460
Exp Brain Res. 1989;76(3):485-96
2792242
Neuroscience. 1995 Jun;66(3):571-81
7644021
Neuropsychobiology. 2000;42(2):51-7
10940758
Neuroscience. 1993 Mar;53(1):23-38
8469309
Hippocampus. 2004;14(1):124-34
15058490
Exp Brain Res. 1989;77(2):309-14
2792278
J Comp Neurol. 1990 Jun 1;296(1):1-22
2358525
Biol Psychiatry. 2006 Jan 15;59(2):155-61
16125145
J Neurosci. 2004 Sep 1;24(35):7648-53
15342731
J Neurosci. 1995 Sep;15(9):6023-34
7666186
Proc Natl Acad Sci U S A. 1986 May;83(9):3027-31
3458260
Hippocampus. 2006;16(9):795-808
16881079
Obesity (Silver Spring). 2006 Aug;14 Suppl 5:259S-265S
17021378
J Neurosci. 1985 May;5(5):1222-7
3998818
Behav Brain Res. 1983 Feb;7(2):133-53
6830648
J Neurosci. 1995 Jan;15(1 Pt 1):61-9
7823152
J Comp Neurol. 1988 Dec 15;278(3):344-52
3216047
Brain Res. 1990 Oct 29;531(1-2):225-31
1705153
Stress. 2006 Mar;9(1):1-11
16753928
Curr Opin Neurobiol. 2006 Dec;16(6):701-9
17084616
Exp Brain Res. 1992;88(1):91-105
1371756
Brain Res. 1990 Mar 26;512(1):113-20
2337798
Science. 1985 Sep 27;229(4720):1397-400
4035356
Neurobiol Aging. 2006 Apr;27(4):645-54
15953661
J Neurosci Res. 2006 Mar;83(4):525-31
16447268
Neurobiol Aging. 1981 Winter;2(4):265-75
7335145
J Neurophysiol. 1998 Jan;79(1):334-41
9425202
Nat Clin Pract Endocrinol Metab. 2007 Feb;3(2):168-79
17237843
Eur J Neurosci. 2006 Jul;24(2):595-605
16903861
Neuropathology. 2006 Dec;26(6):508-18
17203586
Behav Neurosci. 1984 Dec;98(6):946-54
6439229
Science. 1981 Oct 30;214(4520):581-4
6270791
Nature. 1996 Jan 18;379(6562):255-7
8538790
Ageing Res Rev. 2005 May;4(2):123-40
15964248
Aging Clin Exp Res. 2006 Apr;18(2):167-70
16702789