Inhibitory Interneuron Deficit Links Altered Network Activity and Cognitive Dysfunction in Alzheimer Model

被引：890

作者：

Verret, Laure ^{[1
,2
]}

Mann, Edward O. ^{[5
]}

Hang, Giao B. ^{[1
,2
]}

Barth, Albert M. I. ^{[5
]}

Cobos, Inma ^{[3
]}

Ho, Kaitlyn ^{[1
]}

Devidze, Nino ^{[1
]}

Masliah, Eliezer ^{[6
]}

Kreitzer, Anatol C. ^{[1
,2
,4
]}

Mody, Istvan ^{[5
]}

Mucke, Lennart ^{[1
,2
]}

Palop, Jorge J. ^{[1
,2
]}

机构：

[1] Gladstone Inst Neurol Dis, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA

[3] Univ Calif San Francisco, Nina Ireland Lab Dev Neurobiol, San Francisco, CA 94158 USA

[4] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA

[5] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA

[6] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92093 USA

来源：

CELL | 2012年 / 149卷 / 03期

基金：

美国国家卫生研究院;

关键词：

INDUCED NEURONAL DYSFUNCTION; DISEASE MOUSE MODELS; TRANSGENIC MICE; HIPPOCAMPAL NETWORK; GAMMA-OSCILLATIONS; FEBRILE SEIZURES; SCN1A GENE; IN-VIVO; EPILEPSY; MUTATIONS;

D O I：

10.1016/j.cell.2012.02.046

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Alzheimer's disease (AD) results in cognitive decline and altered network activity, but the mechanisms are unknown. We studied human amyloid precursor protein (hAPP) transgenic mice, which simulate key aspects of AD. Electroencephalographic recordings in hAPP mice revealed spontaneous epileptiform discharges, indicating network hypersynchrony, primarily during reduced gamma oscillatory activity. Because this oscillatory rhythm is generated by inhibitory parvalbumin (PV) cells, network dysfunction in hAPP mice might arise from impaired PV cells. Supporting this hypothesis, hAPP mice and AD patients had decreased levels of the interneuron-specific and PV cell-predominant voltage-gated sodium channel subunit Nav1.1. Restoring Nav1.1 levels in hAPP mice by Nav1.1-BAC expression increased inhibitory synaptic activity and gamma oscillations and reduced hypersynchrony, memory deficits, and premature mortality. We conclude that reduced Nav1.1 levels and PV cell dysfunction critically contribute to abnormalities in oscillatory rhythms, network synchrony, and memory in hAPP mice and possibly in AD.

引用

页码：708 / 721

页数：14

共 55 条

[41] Reducing endogenous tau ameliorates amyloid β-induced deficits in an Alzheimer's disease mouse model [J].

Roberson, Erik D. ;

Scearce-Levie, Kimberly ;

Palop, Jorge J. ;

Yan, Fengrong ;

Cheng, Irene H. ;

Wu, Tiffany ;

Gerstein, Hilary ;

Yu, Gui-Qiu ;

Mucke, Lennart .

SCIENCE, 2007, 316 (5825) :750-754

[42] Amyloid-β/Fyn-Induced Synaptic, Network, and Cognitive Impairments Depend on Tau Levels in Multiple Mouse Models of Alzheimer's Disease [J].

Roberson, Erik D. ;

Halabisky, Brian ;

Yoo, Jong W. ;

Yao, Jinghua ;

Chin, Jeannie ;

Yan, Fengrong ;

Wu, Tiffany ;

Hamto, Patricia ;

Devidze, Nino ;

Yu, Gui-Qiu ;

Palop, Jorge J. ;

Noebels, Jeffrey L. ;

Mucke, Lennart .

JOURNAL OF NEUROSCIENCE, 2011, 31 (02) :700-711

[43] Hippocampal and neocortical gamma oscillations predict memory formation in humans [J].

Sederberg, Per B. ;

Schulze-Bonhage, Andreas ;

Madsen, Joseph R. ;

Bromfield, Edward B. ;

McCarthy, David C. ;

Brandt, Armin ;

Tully, Michele S. ;

Kahana, Michael J. .

CEREBRAL CORTEX, 2007, 17 (05) :1190-1196

[44] Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life [J].

Snider, BJ ;

Norton, J ;

Coats, MA ;

Chakraverty, S ;

Hou, CE ;

Jervis, R ;

Lendon, CL ;

Goate, AM ;

McKeel, DW ;

Morris, JC .

ARCHIVES OF NEUROLOGY, 2005, 62 (12) :1821-1830

[45] Parvalbumin neurons and gamma rhythms enhance cortical circuit performance [J].

Sohal, Vikaas S. ;

Zhang, Feng ;

Yizhar, Ofer ;

Deisseroth, Karl .

NATURE, 2009, 459 (7247) :698-702

[46] Lamotrigine derivatives and riluzole inhibit INa,P in cortical neurons [J].

Spadoni, F ;

Hainsworth, AH ;

Mercuri, NB ;

Caputi, L ;

Martella, G ;

Lavaroni, F ;

Bernardi, G ;

Stefani, A .

NEUROREPORT, 2002, 13 (09) :1167-1170

[47] Amyloid Deposition Is Associated with Impaired Default Network Function in Older Persons without Dementia [J].

Sperling, Reisa A. ;

LaViolette, Peter S. ;

O'Keefe, Kelly ;

O'Brien, Jacqueline ;

Rentz, Dorene M. ;

Pihlajamaki, Maija ;

Marshall, Gad ;

Hyman, Bradley T. ;

Selkoe, Dennis J. ;

Hedden, Trey ;

Buckner, Randy L. ;

Becker, J. Alex ;

Johnson, Keith A. .

NEURON, 2009, 63 (02) :178-188

[48] Refractory, life-threatening status epilepticus in a 3-year-old girl [J].

Striano, Pasquale ;

Striano, Salvatore ;

Minetti, Carlo ;

Zara, Federico .

LANCET NEUROLOGY, 2008, 7 (03) :278-284

[49] Microdeletions involving the SCN1A gene may be common in SCN1A-mutation-negative SMEI patients [J].

Suls, Arvid ;

Claeys, Kristl G. ;

Goossens, Dirk ;

Harding, Boris ;

Van Luijk, Rob ;

Scheers, Stefaan ;

Deprez, Liesbet ;

Audenaert, Dominique ;

Van Dyck, Tine ;

Beeckmans, Sabine ;

Smouts, Iris ;

Ceulemans, Berten ;

Lagae, Lieven ;

Buyse, Gunnar ;

Barisic, Nina ;

Misson, Jean-Paul ;

Wauters, Jan ;

Del-Favero, Jurgen ;

De Jonghe, Peter ;

Claes, Lieve R. E. .

HUMAN MUTATION, 2006, 27 (09) :914-920

[50] A BAC transgenic mouse model reveals neuron subtype-specific effects of a Generalized Epilepsy with Febrile Seizures Plus (GEFS plus ) mutation [J].

Tang, Bin ;

Dutt, Karoni ;

Papale, Ligia ;

Rusconi, Raffaella ;

Shankar, Anupama ;

Hunter, Jessica ;

Tufik, Sergio ;

Yu, Frank H. ;

Catterall, William A. ;

Mantegazza, Massimo ;

Goldin, Alan L. ;

Escayg, Andrew .

NEUROBIOLOGY OF DISEASE, 2009, 35 (01) :91-102

← 1 2 3 4 5 6 →