Dendritic pathology in mental retardation: from molecular genetics to neurobiology

Genes, Brain and Behavior - Tập 5 Số s2 - Trang 48-60 - 2006
Mara Dierssen1, G.J.A. Ramakers2
1Neurobehavioral Analysis Laboratory, Genes and Disease Program, Center for Genomic Regulation, (CRG-UPF) PRBB, 08003 Barcelona, Spain.
2Neurons and Networks, Netherlands Institute for Brain Research, Graduate School Neurosciences Amsterdam, Meibergdreef 33, 1105 AZ Amsterdam ZO, The Netherlands

Tóm tắt

Mental retardation (MR) is a developmental brain disorder characterized by impaired cognitive performance and adaptive skills that affects 1–2% of the population. During the last decade, a large number of genes have been cloned that cause MR upon mutation in humans. The causal role of these genes provides an excellent starting point to investigate the cellular, neurobiological and behavioral alterations and mechanisms responsible for the cognitive impairment in mentally retarded persons. However, studies on Down syndrome (DS) reveal that overexpression of a cluster of genes and various forms of MR that are caused by single‐gene mutations, such as fragile X (FraX), Rett, Coffin‐Lowry, Rubinstein–Taybi syndrome and non‐syndromic forms of MR, causes similar phenotypes. In spite of the many differences in the manifestation of these forms of MR, evidence converges on the proposal that MR is primarily due to deficiencies in neuronal network connectivity in the major cognitive centers in the brain, which secondarily results in impaired information processing. Although MR has been largely regarded as a brain disorder that cannot be cured, our increased understanding of the abnormalities and mechanisms underlying MR may provide an avenue for the development of therapies for MR. In this review, we discuss the neurobiology underlying MR, with a focus on FraX and DS

Từ khóa


Tài liệu tham khảo

Anneren G., 1993, Down syndrome – a gene dosage disease caused by trisomy of genes within a small segment of the long arm of chromosome 21, exemplified by the study of effects from the superoxide‐dismutase type 1 (SOD‐1) Gene, APMIS Suppl, 40, 71

10.1038/nrg1448

10.1002/jnr.490380205

10.1006/brln.1994.1001

10.1113/jphysiol.1984.sp015312

10.1006/excr.2000.4932

Balogh E.Z., 2002, Cerebral glucose metabolism in Down syndrome using positron emission tomography, Orv Hetil, 143, 1304

10.1523/JNEUROSCI.04-08-01944.1984

10.1007/BF00692698

10.1002/ana.410200413

Becker L., 1991, Growth and development of the brain in Down syndrome, Prog Clin Biol Res, 373, 133

10.1002/cne.20337

10.1016/j.pneurobio.2004.08.001

10.1016/j.nbd.2005.02.004

10.1542/peds.104.2.e21

10.1016/S0896-6273(02)00906-6

10.1016/S0092-8674(01)00568-2

10.1073/pnas.93.15.8040

Cairns N.J., 2001, Molecular neuropathology of transgenic mouse models of Down syndrome, J Neural Transm suppl, 61, 289

10.1074/jbc.M506205200

10.1016/S0960-9822(02)01352-0

10.1093/hmg/ddg350

10.1038/35088558

10.1074/jbc.M111101200

10.1097/00008480-200012000-00003

10.1002/ajmg.a.20007

10.1073/pnas.94.10.5401

10.1111/j.1469-7610.2004.t01-1-00297.x

10.1016/0361-9230(86)90074-2

10.1002/(SICI)1096-8628(19971112)72:4<468::AID-AJMG18>3.0.CO;2-P

10.1016/S0092-8674(01)00566-9

10.1101/gad.1276805

10.1038/ng0193-31

10.1002/cne.902920108

10.1093/cercor/13.7.758

Dolen G., 2005, Courting a cure for fragile X, Neuron, 45, 642, 10.1016/j.neuron.2005.02.021

Dutch‐Belgian Fragile X Consortium., 1994, Fmr1 knockout mice: a model to study FraX mental retardation, Cell, 78, 23

10.1016/S0079-6123(02)36012-6

10.1038/19978

10.1016/0304-3940(95)12052-6

10.1016/S0304-3940(98)00317-6

10.1523/JNEUROSCI.17-05-01539.1997

10.1016/S1097-2765(00)80012-X

10.1007/BF00294247

10.1016/S0896-6273(00)80467-5

10.1038/78791

Flórez J., 1992, Biomedical Concerns in Persons with Down Syndrome, 159

Friedlander M.J., 1982, Effects of monocular deprivation on the structure–function relationship of individual neurons in the cat's lateral geniculate nucleus, J Neurosci, 2, 321, 10.1523/JNEUROSCI.02-03-00321.1982

10.1034/j.1399-0004.2002.620601.x

10.1016/0022-510X(87)90095-5

10.1016/S0006-8993(03)02363-1

10.1002/(SICI)1096-8628(19960809)64:2<246::AID-AJMG2>3.0.CO;2-S

10.1073/pnas.141145998

10.1038/nature01276

10.1016/S0959-4388(99)80050-6

10.1523/JNEUROSCI.09-08-02982.1989

10.1126/science.290.5492.739

10.1523/JNEUROSCI.19-10-03918.1999

10.1002/ajmg.1320410306

10.1016/0014-4886(81)90160-6

10.1073/pnas.122205699

10.1212/WNL.24.3.203

10.1016/0028-3932(90)90031-I

10.1002/1096-8628(20010115)98:2<161::AID-AJMG1025>3.0.CO;2-B

10.1002/ajmg.10500

10.1006/nlme.1997.3774

Jyothy A., 2002, Translocation Down syndrome, Indian J Med Sci, 56, 225

10.1016/S0166-2236(03)00162-0

10.1093/cercor/10.10.981

10.1016/S0168-9525(03)00017-9

Kossel A., 1995, Relationships between dendritic fields and functional architecture in striate cortex of normal and visually deprived cats, J Neurosci, 15, 3913, 10.1523/JNEUROSCI.15-05-03913.1995

10.1038/35009107

10.1006/mcne.2001.1085

10.1038/35044547

10.1038/382363a0

10.1126/science.283.5409.1923

10.1016/0006-8993(72)90324-1

10.1002/cne.901670105

Massey P.S., 1995, State‐specific rates of mental retardation – United States, 1993, MMWR, 45, 61

10.1038/nn736

10.1126/science.290.5492.754

10.1016/j.neuron.2005.01.038

McDermott S., 1994, Explanatory model to describe school district prevalence rates for mental retardation and learning disabilities, Am J Ment Retard, 99, 175

10.1044/1092-4388(2005/013)

10.1016/S0896-6273(03)00034-5

10.1111/j.1528-1157.1999.tb00824.x

10.1034/j.1601-183X.2003.00026.x

10.1016/j.pnpbp.2004.12.009

10.1523/JNEUROSCI.21-14-05139.2001

10.1016/j.cub.2004.09.085

10.1016/S0306-4522(99)00285-7

10.1093/hmg/9.8.1145

Pope A.M., 1991, Disability in America: Toward a National Agenda for Prevention.

Prinz M., 1997, The growth of non‐pyramidal neurons in the primary motor cortex of man: a Golgi study, Histol Histopathol, 12, 895

10.1038/sj.ejhg.5200356

10.1016/S0014-5793(00)01793-2

10.1126/science.186.4169.1126

10.1002/1096-8628(20001023)94:5<367::AID-AJMG4>3.0.CO;2-I

10.1016/S0166-2236(00)02118-4

10.1212/WNL.45.2.356

10.1097/00005072-199909000-00004

10.1038/nm0295-159

10.1093/emboj/20.17.4803

Schulz E., 1992, Neurohistological findings in the parietal cortex of children with chromosome aberrations, J irnforsch, 33, 37

10.1016/0166-2236(95)92765-I

10.1016/j.brainres.2004.05.100

10.1152/jn.1996.75.6.2197

10.1128/MCB.22.24.8438-8447.2002

10.1002/mrdd.20011

10.1523/JNEUROSCI.18-02-00658.1998

10.1016/S0896-6273(02)00652-9

10.3104/reviews.118

10.1016/0165-3806(83)90206-7

10.1007/BF00688755

10.1016/0006-8993(81)90314-0

10.1016/S0387-7604(89)80082-8

10.1111/j.1365-2788.1994.tb00394.x

10.1016/j.mehy.2004.08.020

10.1093/cercor/10.10.939

10.1038/46574

10.1038/nature01273

10.1007/s00335-004-2428-7

10.1152/jn.1999.82.1.450

10.1016/S0887-8994(02)00380-6

10.1073/pnas.0407533101

Wisniewski K.E., 1994, Abnormal neurogenesis and synaptogenesis in Down syndrome brain, Dev Brain Dysfunct, 7, 289

10.1074/jbc.M104091200

10.1016/S0896-6273(00)80091-4

10.1016/S0092-8674(01)00589-X

10.1016/S0896-6273(00)80283-4

Thông tin
Thông tin xuất bản

Genes, Brain and Behavior

Tập 5 Số s2

48-60

Thông tin tác giả