Do glia drive synaptic and cognitive impairment in disease?

被引：286

作者：

Chung, Won-Suk ^{[1
]}

Welsh, Christina A. ^{[2
]}

Barres, Ben A. ^{[1
]}

Stevens, Beth ^{[2
]}

机构：

[1] Stanford Univ, Sch Med, Dept Neurobiol, Palo Alto, CA 94304 USA

[2] Harvard Univ, Sch Med, Dept Neurol, FM Kirby Neurobiol Ctr,Boston Childrens Hosp, Boston, MA 02115 USA

来源：

NATURE NEUROSCIENCE | 2015年 / 18卷 / 11期

关键词：

ASTROCYTE-SECRETED PROTEINS; ALZHEIMERS-DISEASE; MOUSE MODELS; COMPLEMENT ACTIVATION; MICROGLIAL RESPONSE; CNS SYNAPTOGENESIS; CELLS; TREM2; PATHOLOGY; DEMENTIA;

D O I：

10.1038/nn.4142

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Synaptic dysfunction is a hallmark of many neurodegenerative and psychiatric brain disorders, yet we know little about the mechanisms that underlie synaptic vulnerability. Although neuroinflammation and reactive gliosis are prominent in virtually every CNS disease, glia are largely viewed as passive responders to neuronal damage rather than drivers of synaptic dysfunction. This perspective is changing with the growing realization that glia actively signal with neurons and influence synaptic development, transmission and plasticity through an array of secreted and contact-dependent signals. We propose that disruptions in neuron-glia signaling contribute to synaptic and cognitive impairment in disease. Illuminating the mechanisms by which glia influence synapse function may lead to the development of new therapies and biomarkers for synaptic dysfunction.

引用

页码：1539 / 1545

页数：7

共 77 条

[1] Astroglial Glutamate Transporter Deficiency Increases Synaptic Excitability and Leads to Pathological Repetitive Behaviors in Mice [J].

Aida, Tomomi ;

Yoshida, Junichi ;

Nomura, Masatoshi ;

Tanimura, Asami ;

Iino, Yusuke ;

Soma, Miho ;

Bai, Ning ;

Ito, Yukiko ;

Cui, Wanpeng ;

Aizawa, Hidenori ;

Yanagisawa, Michiko ;

Nagai, Terumi ;

Takata, Norio ;

Tanaka, Kenji F. ;

Takayanagi, Ryoichi ;

Kano, Masanobu ;

Goetz, Magdalena ;

Hirase, Hajime ;

Tanaka, Kohichi .

NEUROPSYCHOPHARMACOLOGY, 2015, 40 (07) :1569-1579

[2] Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors [J].

Allen, Nicola J. ;

Bennett, Mariko L. ;

Foo, Lynette C. ;

Wang, Gordon X. ;

Chakraborty, Chandrani ;

Smith, Stephen J. ;

Barres, Ben A. .

NATURE, 2012, 486 (7403) :410-+

[3] Human apoE Isoforms Differentially Regulate Brain Amyloid-β Peptide Clearance [J].

Castellano, Joseph M. ;

Kim, Jungsu ;

Stewart, Floy R. ;

Jiang, Hong ;

DeMattos, Ronald B. ;

Patterson, Bruce W. ;

Fagan, Anne M. ;

Morris, John C. ;

Mawuenyega, Kwasi G. ;

Cruchaga, Carlos ;

Goate, Alison M. ;

Bales, Kelly R. ;

Paul, Steven M. ;

Bateman, Randall J. ;

Holtzman, David M. .

SCIENCE TRANSLATIONAL MEDICINE, 2011, 3 (89)

[4] Apoptotic Engulfment Pathway and Schizophrenia [J].

Chen, Xiangning ;

Sun, Cuie ;

Chen, Qi ;

O'Neill, F. Anthony ;

Walsh, Dermot ;

Fanous, Ayman H. ;

Chowdari, Kodavali V. ;

Nimgaonkar, Vishwajit L. ;

Scott, Adrian ;

Schwab, Sibylle G. ;

Wildenauer, Dieter B. ;

Che, Ronglin ;

Tang, Wei ;

Shi, Yongyong ;

He, Lin ;

Luo, Xiong-jian ;

Su, Bing ;

Edwards, Todd L. ;

Zhao, Zhongming ;

Kendler, Kenneth S. .

PLOS ONE, 2009, 4 (09)

[5] Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis [J].

Christopherson, KS ;

Ullian, EM ;

Stokes, CCA ;

Mullowney, CE ;

Hell, JW ;

Agah, A ;

Lawler, J ;

Mosher, DF ;

Bornstein, P ;

Barres, BA .

CELL, 2005, 120 (03) :421-433

[6] Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways [J].

Chung, Won-Suk ;

Clarke, Laura E. ;

Wang, Gordon X. ;

Stafford, Benjamin K. ;

Sher, Alexander ;

Chakraborty, Chandrani ;

Joung, Julia ;

Foo, Lynette C. ;

Thompson, Andrew ;

Chen, Chinfei ;

Smith, Stephen J. ;

Barres, Ben A. .

NATURE, 2013, 504 (7480) :394-+

[7] Emerging roles of astrocytes in neural circuit development [J].

Clarke, Laura E. ;

Barres, Ben A. .

NATURE REVIEWS NEUROSCIENCE, 2013, 14 (05) :311-321

[8] Trems in the immune system and beyond [J].

Colonna, M .

NATURE REVIEWS IMMUNOLOGY, 2003, 3 (06) :445-453

[9] Structural correlates of cognition in dementia: Quantification and assessment of synapse change [J].

DeKosky, ST ;

Scheff, SW ;

Styren, SD .

NEURODEGENERATION, 1996, 5 (04) :417-421

[10] Wild-type microglia arrest pathology in a mouse model of Rett syndrome [J].

Derecki, Noel C. ;

Cronk, James C. ;

Lu, Zhenjie ;

Xu, Eric ;

Abbott, Stephen B. G. ;

Guyenet, Patrice G. ;

Kipnis, Jonathan .

NATURE, 2012, 484 (7392) :105-+

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