利用基因芯片检测大鼠衰老相关的记忆障碍的调控基因

张双; 王琳; 董素珍

利用基因芯片检测大鼠衰老相关的记忆障碍的调控基因

1.
华东师范大学脑功能基因组学教育部、上海市重点实验室, 上海 200062

详细信息

中图分类号: Q189
计量
- 文章访问数: 2237
- HTML全文浏览量: 14
- PDF下载量: 2085
- 被引次数: 0
出版历程
- 收稿日期: 2010-11-01
- 修回日期: 2011-02-01
- 刊出日期: 2011-11-25

Identification of genes associated with age-related memory impairment in rats

1.
Key Laboratory of Brain Functional Genomics, Ministry of Education &Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062, China

摘要

摘要: 许多证据表明，正常衰老过程伴随着记忆里的衰退。但有些动物却不表现出这种年龄相关的记忆障碍。为了检测其中的分子机制，将24个月的老年大鼠按在水迷宫中的行为表现分成记忆损伤组和记忆未损伤组，分别取海马和内嗅皮层进行基因芯片检测。结果显示，在海马和内嗅皮层中分别由47和37个基因的表达发生了显著变化。但两个脑区的基因表达变化模式却有明显的不同。对差异表达的基因进行功能分析，主要是与结构组织、突触传递、信号转导、转录及免疫和氧化信号相关的基因。这些基因和信号通路可能在记忆的调控过程中起重要作用。该结果为进一步揭示衰老相关的记忆衰退过程的分子机制提供了重要的信息。
- 基因 /
- 记忆障碍 /
- 衰老 /
- 突触传递
Abstract: A large body of evidence indicates that memory impairment is associated with normal aging. Interestingly, some older individuals do not show any memory loss. To understand the molecular mechanisms of the age-related memory disorder, gene expression profiles of hippocampus and entorhinal cortex from 24-month-old memory-impaired and maze were examined using high-density DNA microarrays. The results demonstrated that 47 genes in the hippocampus and 37 genes in the entorhinal cortex showed dynamic changes in their expressions levels. Surprisingly, the overall patterns of gene expression changes in these two brain regions were significantly different. Nevertheless, a number of key genes involved in structure organization, neurotransmission, signaling transduction, transcription, immunity and oxidative signaling were differently expressed in both brain regions. These genes and signal pathways may play essential roles in the regulation of memory. Our results provided important information for understanding the molecular mechanism of age-related memory impairment.
- genes /
- memory impairment /
- aging /
- neurotransmission

HTML全文

参考文献(1)

[1]

?[ 1 ] FORSTER M J, DUBEY A, DAWSON K M, et al. Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain[J]. Proc Natl Acad Sci USA, 1996, 93(10): 4765-4769.

[ 2 ] FRICK K M, BURLINGAME L A, ARTERS J A, et al. Reference memory, anxiety and estrous cyclicity in C57BL/6NIA mice are affected by age and sex[J]. Neuroscience, 2000, 95(1): 293-307.

[ 3 ] STOELZEL C R, STAVNEZER A J, DENENBERG V H, et al. The effects of aging and dorsal hippocampal lesions: performance on spatial and nonspatial comparable versions of the water maze[J]. Neurobiol Learn Mem, 2002, 78(2): 217-233.

[ 4 ] AITKEN D HMEANEY M J. Temporally graded, age-related impairments in spatial memory in the rat[J]. Neurobiol Aging, 1989, 10(3): 273-276.

[ 5 ] MOSS M B, ROSENE D LPETERS A. Effects of aging on visual recognition memory in the rhesus monkey[J]. Neurobiol Aging, 1988, 9(5-6): 495-502.

[ 6 ] RAPP P RAMARAL D G. Evidence for task-dependent memory dysfunction in the aged monkey[J]. J Neurosci, 1989, 9(10): 3568-3576.

[ 7 ] GRADY C LCRAIK F I. Changes in memory processing with age[J]. Curr Opin Neurobiol, 2000, 10(2): 224-231.

[ 8 ] COLLIE A, MARUFF P, SHAFIQ-ANTONACCI R, et al. Memory decline in healthy older people: implications for identifying mild cognitive impairment[J]. Neurology, 2001, 56(11): 1533-1538.

[ 9 ] MIYAGAWA H, HASEGAWA M, FUKUTA T, et al. Dissociation of impairment between spatial memory, and motor function and emotional behavior in aged rats[J]. Behav Brain Res, 1998, 91(1-2): 73-81.

[10] LAW A, DORE S, BLACKSHAW S, et al. Alteration of expression levels of neuronal nitric oxide synthase and haem oxygenase-2 messenger RNA in the hippocampi and cortices of young adult and aged cognitively unimpaired and impaired Long-Evans rats[J]. Neuroscience, 2000, 100(4): 769-775.

[11] BOURTCHOULADZE R, ABEL T, BERMAN N, et al. Different training procedures recruit either one or two critical periods for contextual memory consolidation, each of which requires protein synthesis and PKA[J]. Learn Mem, 1998, 5(4-5): 365-374.

[12] MARTIN K C, CASADIO A, ZHU H, et al. Synapse-specific, long-term facilitation of aplysia sensory to motor synapses: a function for local protein synthesis in memory storage[J]. Cell, 1997, 91(7): 927-938.

?[13] TULLY T. Regulation of gene expression and its role in long-term memory and synaptic plasticity[J]. Proc Natl Acad Sci USA, 1997, 94(9): 4239-4241.

[14] MANSUY I M, MAYFORD M, JACOB B, et al. Restricted and regulated overexpression reveals calcineurin as a key component in the transition from short-term to long-term memory[J]. Cell, 1998, 92(1): 39-49.

[15] IRWIN L N. Gene expression in the hippocampus of behaviorally stimulated rats: analysis by DNA microarray[J]. Brain Res Mol Brain Res, 2001, 96(1-2): 163-169.

[16] CAVALLARO S, DAGATA VALKON D L. Programs of gene expression during the laying down of memory formation as revealed by DNA microarrays[J]. Neurochem Res, 2002, 27(10): 1201-1207.

[17] BLALOCK E M, CHEN K C, SHARROW K, et al. Gene microarrays in hippocampal aging: statistical profiling identifies novel processes correlated with cognitive impairment[J]. J Neurosci, 2003, 23(9): 3807-3819.

[18] VERBITSKY M, YONAN A L, MALLERET G, et al. Altered hippocampal transcript profile accompanies an age-related spatial memory deficit in mice[J]. Learn Mem, 2004, 11(3): 253-260.

[19] DELLA-MAGGIORE V, SEKULER A B, GRADY C L, et al. Corticolimbic interactions associated with per-formance on a short-term memory task are modified by age[J]. J Neurosci, 2000, 20(22): 8410-8416.

[20] MITCHELL K J, JOHNSON M K, RAYE C L, et al. fMRI evidence of age-related hippocampal dysfunction in feature binding in working memory[J]. Brain Res Cogn Brain Res, 2000, 10(1-2): 197-206.

[21] MERRILL D A, CHIBA A ATUSZYNSKI M H. Conservation of neuronal number and size in the entorhinal cortex of behaviorally characterized aged rats[J]. J Comp Neurol, 2001, 438(4): 445-456.

[22] MODY M, CAO Y, CUI Z, et al. Genome-wide gene expression profiles of the developing mouse hippocampus[J]. Proc Natl Acad Sci USA, 2001, 98(15): 8862-8867.

[23] JANZ R, HOFMANN KSUDHOF T C. SVOP, an evolutionarily conserved synaptic vesicle protein, suggests novel transport functions of synaptic vesicles[J]. J Neurosci, 1998, 18(22): 9269-9281.

[24] KABEYA K, ISHIKAWA K, KATAKAI K, et al. Prostaglandin-D-synthase (beta-trace protein) levels in rat cerebrospinal fluid[J]. Neuroreport, 1998, 9(5): 915-919.

[25] HARADA A, TENG J, TAKEI Y, et al. MAP2 is required for dendrite elongation, PKA anchoring in dendrites, and proper PKA signal transduction[J]. J Cell Biol, 2002, 158(3): 541-549.

[26] MEI B, LI C, DONG S, et al. Distinct gene expression profiles in hippocampus and amygdala after fear condi-tioning[J]. Brain Res Bull, 2005, 67(1-2): 1-12.

[27] WANG J, TUNG Y C, WANG Y, et al. Hyperphosphorylation and accumulation of neurofilament proteins in Alzheimer disease brain and in okadaic acid-treated SY5Y cells[J]. FEBS Lett, 2001, 507(1): 81-87.

[28] HASHIMOTO R, NAKAMURA Y, KOMAI S, et al. Site-specific phosphorylation of neurofilament-L is mediated by calcium/calmodulin-dependent protein kinase II in the apical dendrites during long-term potentiation[J]. J

Neurochem, 2000, 75(1): 373-382.

[29] HASHIMOTO R, NAKAMURA Y, KOMAI S, et al. Phosphorylation of neurofilament-L during LTD[J]. Neu-roreport, 2000, 11(12): 2739-2742.

[30] MEI B, LI C, DONG S, et al. Distinct gene expression profiles in hippocampus and amygdala after fear condi-tioning[J]. Brain Research Bulletin, 2005, 67(1-2): 1-12.

[31] BUHOT M C, MARTIN SSEGU L. Role of serotonin in memory impairment[J]. Ann Med, 2000, 32(3): 210-221.

[32] MENESES A. Involvement of 5-HT(2A/2B/2C) receptors on memory formation: simple agonism, antagonism, or inverse agonism?[J]. Cell Mol Neurobiol, 2002, 22(5-6): 675-688.

[33] PABST S, MARGITTAI M, VAINIUS D, et al. Rapid and selective binding to the synaptic SNARE complex suggests a modulatory role of complexins in neuroexocytosis[J]. J Biol Chem, 2002, 277(10): 7838-7848.

[34] TAKEUCHI M, HATA Y, HIRAO K, et al. SAPAPs, a family of PSD-95/SAP90-associated proteins localized at postsynaptic density[J]. J Biol Chem, 1997, 272(18): 11943-11951.

[35] KITRAKI E, BOZAS E, PHILIPPIDIS H, et al. Aging-related changes in IGF-II and c-fos gene expression in the rat brain[J]. Int J Dev Neurosci, 1993, 11(1): 1-9.

[36] LAI M, HIBBERD C J, GLUCKMAN P D, et al. Reduced expression of insulin-like growth factor 1 messenger RNA in the hippocampus of aged rats[J]. Neurosci Lett, 2000, 288(1): 66-70.

[37] MARKOWSKA A L, MOONEY MSONNTAG W E. Insulin-like growth factor-1 ameliorates age-related behav-ioral deficits[J]. Neuroscience, 1998, 87(3): 559-569.

[38] DIK M G, PLUIJM S M, JONKER C, et al. Insulin-like growth factor I (IGF-I) and cognitive decline in older persons[J]. Neurobiol Aging, 2003, 24(4): 573-581.

[39] TU J C, XIAO B, YUAN J P, et al. Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors[J]. Neuron, 1998, 21(4): 717-726.

[40] CHEN F, OGAWA K, LIU X, et al. Repression of Smad2 and Smad3 transactivating activity by association with a novel splice variant of CCAAT-binding factor C subunit[J]. Biochem J, 2002, 364(Pt 2): 571-577.

施引文献

资源附件(0)

访问统计