Transgenic mice overexpressing reticulon 3 develop neuritic abnormalities

被引：105

作者：

Xiangyou Hu ^{[1
]}

Qi Shi ^{[1
]}

Xiangdong Zhou ^{[1
]}

Wanxia He ^{[1
]}

Hong Yi ^{[2
]}

Xinghua Yin ^{[1
]}

Marla Gearing ^{[3
]}

Allan Levey ^{[3
]}

Riqiang Yan ^{[1
]}

机构：

[1] Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH

[2] Microscopy Core, Emory University, School of Medicine, Atlanta, GA

[3] Department of Neurology, Emory University, School of Medicine, Atlanta, GA

[4] Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195

来源：

The EMBO Journal | 2007年 / 26卷 / 11期

关键词：

BACE1; Diffuse plaques; Dystrophic neurites; Nogo; Reticulon;

D O I：

10.1038/sj.emboj.7601707

中图分类号：

学科分类号：

摘要：

Dystrophic neurites are swollen dendrites or axons recognizable near amyloid plaques as a part of important pathological feature of Alzheimer's disease (AD). We report herein that reticulon 3 (RTN3) is accumulated in a distinct population of dystrophic neurites named as RTN3 immunoreactive dystrophic neurites (RIDNs). The occurrence of RIDNs is concomitant with the formation of high-molecular-weight RTN3 aggregates in brains of AD cases and mice expressing mutant APP. Ultrastructural analysis confirms accumulation of RTN3-containing aggregates in RIDNs. It appears that the protein level of RTN3 governs the formation of RIDNs because transgenic mice expressing RTN3 will develop RIDNs, initially in the hippocampal CA1 region, and later in other hippocampal and cortical regions. Importantly, we show that the presence of dystrophic neurites in Tg-RTN3 mice causes impairments in spatial learning and memory, as well as synaptic plasticity, implying that RIDNs potentially contribute to AD cognitive dysfunction. Together, we demonstrate that aggregation of RTN3 contributes to AD pathogenesis by inducing neuritic dystrophy. Inhibition of RTN3 aggregation is likely a therapeutic approach for reducing neuritic dystrophy. ©2007 European Molecular Biology Organization.

引用

页码：2755 / 2767

页数：12

共 55 条

[1]

Arroyo-Jim nez M.M., Bourgeois J.P., Marubio L.M., Le Sourd A.M., Ottersen O.P., Rinvik E., Fairen A., Changeux J.P., Ultrastructural localization of the alpha4-subunit of the neuronal acetylcholine nicotinic receptor in the rat substantia nigra, J Neurosci, 19, pp. 6475-6487, (1999)

[2]

Baba A., Yasui T., Fujisawa S., Yamada R.X., Yamada M.K., Nishiyama N., Matsuki N., Ikegaya Y., Activity-evoked capacitative Ca2+ entry: Implications in synaptic plasticity, J Neurosci, 23, pp. 7737-7741, (2003)

[3]

Bach M.E., Hawkins R.D., Osman M., Kandel E.R., Mayford M., Impairment of spatial but not contextual memory in CaMKII mutant mice with a selective loss of hippocampal LTP in the range of the theta frequency, Cell, 81, pp. 905-915, (1995)

[4]

Barnes C.A., Markowska A.L., Ingram D.K., Kametani H., Spangler E.L., Lemken V.J., Olton D.S., Acetyl-1-carnitine. 2: Effects on learning and memory performance of aged rats in simple and complex mazes, Neurobiol Aging, 11, pp. 499-506, (1990)

[5]

Borchelt D.R., Ratovitski T., van Lare J., Lee M.K., Gonzales V., Jenkins N.A., Copeland N.G., Price D.L., Sisodia S.S., Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins, Neuron, 19, pp. 939-945, (1997)

[6]

Brendza R.P., Bacskai B.J., Cirrito J.R., Simmons K.A., Skoch J.M., Klunk W.E., Mathis C.A., Bales K.R., Paul S.M., Hyman B.T., Holtzman D.M., Anti-Abeta antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice, J Clin Invest, 115, pp. 428-433, (2005)

[7]

Couillard-Despres S., Zhu Q., Wong P.C., Price D.L., Cleveland D.W., Julien J.P., Protective effect of neurofilament heavy gene overexpression in motor neuron disease induced by mutant superoxide dismutase, Proc Natl Acad Sci USA, 95, pp. 9626-9630, (1998)

[8]

Crain B.J., Hu W., Sze C.I., Slunt H.H., Koo E.H., Price D.L., Thinakaran G., Sisodia S.S., Expression and distribution of amyloid precursor protein-like protein-2 in Alzheimer's disease and in normal brain, Am J Pathol, 149, pp. 1087-1095, (1996)

[9]

Dickson D.W., Farlo J., Davies P., Crystal H., Fuld P., Yen S.H., Alzheimer's disease. A double-labeling immunohistochemical study of senile plaques, Am J Pathol, 132, pp. 86-101, (1988)

[10]

Dickson T.C., King C.E., McCormack G.H., Vickers J.C., Neurochemical diversity of dystrophic neurites in the early and late stages of Alzheimer's disease, Exp Neurol, 156, pp. 100-110, (1999)

← 1 2 3 4 5 6 →