p75 reduces β-amyloid-induced sympathetic innervation deficits in an Alzheimer's disease mouse model

被引:19
作者
Bengoechea, Tasha G. [1 ]
Chen, Zhijiang [1 ]
O'Leary, Deborah [1 ]
Masliah, Eliezer [2 ]
Lee, Kuo-Fen [1 ]
机构
[1] Salk Inst Biol Studies, Peptide Biol Lab, La Jolla, CA 92037 USA
[2] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
NEUROTROPHIN RECEPTOR; NEURITE OUTGROWTH; PRECURSOR PROTEIN; SMALL-MOLECULE; NOGO RECEPTOR; DORSAL-ROOT; BACE1; P75(NTR); NEURONS; BINDS;
D O I
10.1073/pnas.0901533106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
beta-Amyloid (A beta) has adverse effects on brain cells, but little is known about its effects on the peripheral nervous system in Alzheimer's disease ( AD). Several lines of in vitro evidence suggest that the neurotrophin receptor p75 mediates or exacerbates A beta-induced neurotoxicity. Here, we show that p75-deficient sympathetic neurons are more sensitive to A beta-induced neurite growth inhibition. To investigate the role of p75 in the sympathetic nervous system of AD, p75 mutant mice were crossed with a mouse line of AD model. The majority of p75-deficient AD mice died by 3 weeks of age. The lethality is associated with severe defects in sympathetic innervation to multiple organs. When 1 copy of the BACE1 gene encoding a protein essential in A beta production was deleted in p75-deficient AD mice, sympathetic innervation was significantly restored. These results suggest that p75 is neuroprotective for the sympathetic nervous system in a mouse model of AD.
引用
收藏
页码:7870 / 7875
页数:6
相关论文
共 43 条
[1]   Autonomic dysfunction in dementia [J].
Allan, L. M. ;
Ballard, C. G. ;
Allen, J. ;
Murray, A. ;
Davidson, A. W. ;
McKeith, I. G. ;
Kenny, R. A. .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2007, 78 (07) :671-677
[2]   p75NTR is positively promiscuous: Novel partners and new insights [J].
Barker, PA .
NEURON, 2004, 42 (04) :529-533
[3]  
Bentley CA, 2000, J NEUROSCI, V20, P7706
[4]   IMPAIRED SYMPATHETIC NERVOUS-SYSTEM RESPONSE TO COGNITIVE EFFORT IN EARLY ALZHEIMERS-DISEASE [J].
BORSON, S ;
BARNES, RF ;
VEITH, RC ;
HALTER, JB ;
RASKIND, MA .
JOURNALS OF GERONTOLOGY, 1989, 44 (01) :M8-M12
[5]   The p75 neurotrophin receptor influences NT-3 responsiveness of sympathetic neurons in vivo [J].
Brennan, C ;
Rivas-Plata, K ;
Landis, SC .
NATURE NEUROSCIENCE, 1999, 2 (08) :699-705
[6]   Fyn kinase modulates synaptotoxicity, but not aberrant sprouting, in human amyloid precursor protein transgenic mice [J].
Chin, J ;
Palop, JJ ;
Yu, GQ ;
Kojima, N ;
Masliah, E ;
Mucke, L .
JOURNAL OF NEUROSCIENCE, 2004, 24 (19) :4692-4697
[7]   A century of Alzheimer's disease [J].
Goedert, Michel ;
Spillantini, Maria Grazia .
SCIENCE, 2006, 314 (5800) :777-781
[8]   Activation of Rac GTPase by p75 is necessary for c-jun N-terminal kinase-mediated apoptosis [J].
Harrington, AW ;
Kim, JY ;
Yoon, SO .
JOURNAL OF NEUROSCIENCE, 2002, 22 (01) :156-166
[9]   Bace1 modulates myelination in the central and peripheral nervous system [J].
Hu, Xiangyou ;
Hicks, Caitlin W. ;
He, Wanxia ;
Wong, Philip ;
Macklin, Wendy B. ;
Trapp, Bruce D. ;
Yan, Riqiang .
NATURE NEUROSCIENCE, 2006, 9 (12) :1520-1525
[10]  
Kuner P, 1998, J NEUROSCI RES, V54, P798, DOI 10.1002/(SICI)1097-4547(19981215)54:6<798::AID-JNR7>3.0.CO