Failure of Neuronal Maturation in Alzheimer Disease Dentate Gyrus

Overview

Journal J Neuropathol Exp Neurol

Publisher Oxford University Press

Specialties Neurology
Pathology

Date 2007 Dec 20

PMID 18091557

Citations 107

Authors

Bin Li

Hidenaga Yamamori

Yoshitaka Tatebayashi

Bridget Shafit-Zagardo

Hitoshi Tanimukai

She Chen

Khalid Iqbal

Inge Grundke-Iqbal

Affiliations

Soon will be listed here.

Abstract

The dentate gyrus, an important anatomic structure of the hippocampal formation, is one of the major areas in which neurogenesis takes place in the adult mammalian brain. Neurogenesis in the dentate gyrus is thought to play an important role in hippocampus-dependent learning and memory. Neurogenesis has been reported to be increased in the dentate gyrus of patients with Alzheimer disease, but it is not known whether the newly generated neurons differentiate into mature neurons. In this study, the expression of the mature neuronal marker high molecular weight microtubule-associated protein (MAP) isoforms MAP2a and b was found to be dramatically decreased in Alzheimer disease dentate gyrus, as determined by immunohistochemistry and in situ hybridization. The total MAP2, including expression of the immature neuronal marker, the MAP2c isoform, was less affected. These findings suggest that newly generated neurons in Alzheimer disease dentate gyrus do not become mature neurons, although neuroproliferation is increased.

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References

Shors T, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E . Neurogenesis in the adult is involved in the formation of trace memories. Nature. 2001; 410(6826):372-6. DOI: 10.1038/35066584. View

Chen H, Tung Y, Li B, Iqbal K, Grundke-Iqbal I . Trophic factors counteract elevated FGF-2-induced inhibition of adult neurogenesis. Neurobiol Aging. 2006; 28(8):1148-62. DOI: 10.1016/j.neurobiolaging.2006.05.036. View

Kalcheva N, Dickson D, Davies P, Kress Y . Distribution and subcellular localization of high-molecular-weight microtubule-associated protein-2 expressing exon 8 in brain and spinal cord. J Neurochem. 1997; 68(2):862-73. DOI: 10.1046/j.1471-4159.1997.68020862.x. View

Chung W, Kindler S, Seidenbecher C, Garner C . MAP2a, an alternatively spliced variant of microtubule-associated protein 2. J Neurochem. 1996; 66(3):1273-81. DOI: 10.1046/j.1471-4159.1996.66031273.x. View

Tanimukai H, Grundke-Iqbal I, Iqbal K . Inhibitors of protein phosphatase-2A: topography and subcellular localization. Brain Res Mol Brain Res. 2004; 126(2):146-56. DOI: 10.1016/j.molbrainres.2004.04.003. View

Gould E, Beylin A, Tanapat P, Reeves A, Shors T . Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci. 1999; 2(3):260-5. DOI: 10.1038/6365. View

Grundke-Iqbal I, Iqbal K, Tung Y, Quinlan M, Wisniewski H, Binder L . Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A. 1986; 83(13):4913-7. PMC: 323854. DOI: 10.1073/pnas.83.13.4913. View

Eriksson P, Perfilieva E, Bjork-Eriksson T, Alborn A, Nordborg C, Peterson D . Neurogenesis in the adult human hippocampus. Nat Med. 1998; 4(11):1313-7. DOI: 10.1038/3305. View

Grundke-Iqbal I, Iqbal K, Quinlan M, Tung Y, Zaidi M, Wisniewski H . Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem. 1986; 261(13):6084-9. View

10.

West M, Coleman P, Flood D, Troncoso J . Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease. Lancet. 1994; 344(8925):769-72. DOI: 10.1016/s0140-6736(94)92338-8. View

11.

Kalcheva N, Albala J, OGuin K, RUBINO H, Garner C . Genomic structure of human microtubule-associated protein 2 (MAP-2) and characterization of additional MAP-2 isoforms. Proc Natl Acad Sci U S A. 1995; 92(24):10894-8. PMC: 40537. DOI: 10.1073/pnas.92.24.10894. View

12.

Snyder J, Hong N, McDonald R, Wojtowicz J . A role for adult neurogenesis in spatial long-term memory. Neuroscience. 2005; 130(4):843-52. DOI: 10.1016/j.neuroscience.2004.10.009. View

13.

Imaizumi K, Tsuda M, Wanaka A, Tohyama M, Takagi T . Differential expression of sgk mRNA, a member of the Ser/Thr protein kinase gene family, in rat brain after CNS injury. Brain Res Mol Brain Res. 1994; 26(1-2):189-96. DOI: 10.1016/0169-328x(94)90090-6. View

14.

Wegiel J, Tarnawski M, Bobinski M, Reisberg B, de Leon M, Miller D . Relationships between regional neuronal loss and neurofibrillary changes in the hippocampal formation and duration and severity of Alzheimer disease. J Neuropathol Exp Neurol. 1997; 56(4):414-20. DOI: 10.1097/00005072-199704000-00010. View

15.

Hyman B, Trojanowski J . Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol. 1997; 56(10):1095-7. DOI: 10.1097/00005072-199710000-00002. View

16.

Mirra S, HEYMAN A, McKeel D, SUMI S, Crain B, Brownlee L . The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991; 41(4):479-86. DOI: 10.1212/wnl.41.4.479. View

17.

CRANDALL J, Fischer I . Developmental regulation of microtubule-associated protein 2 expression in regions of mouse brain. J Neurochem. 1989; 53(6):1910-7. DOI: 10.1111/j.1471-4159.1989.tb09261.x. View

18.

Braak H, Braak E . Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991; 82(4):239-59. DOI: 10.1007/BF00308809. View

19.

Einstein G, Buranosky R, Crain B . Dendritic pathology of granule cells in Alzheimer's disease is unrelated to neuritic plaques. J Neurosci. 1994; 14(8):5077-88. PMC: 6577187. View

20.

Jin K, Peel A, Mao X, Xie L, Cottrell B, Henshall D . Increased hippocampal neurogenesis in Alzheimer's disease. Proc Natl Acad Sci U S A. 2003; 101(1):343-7. PMC: 314187. DOI: 10.1073/pnas.2634794100. View