CREB controls cortical circuit plasticity and functional recovery after stroke

被引：100

作者：

Caracciolo, L. ^{[1
]}

Marosi, M. ^{[1
,2
]}

Mazzitelli, J. ^{[1
]}

Latifi, S. ^{[1
]}

Sano, Y. ^{[2
,3
,4
,5
,6
]}

Galvan, L. ^{[4
]}

Kawaguchi, R. ^{[7
,8
]}

Holley, S. ^{[4
]}

Levine, M. S. ^{[4
]}

Coppola, G. ^{[7
,8
]}

Portera-Cailliau, C. ^{[1
,2
]}

Silva, A. J. ^{[2
,3
,4
,5
,6
]}

Carmichael, S. T. ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychol, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, Integrat Ctr Learning & Memory, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, David Geffen Sch Med, Program Neurogenet, Dept Neurol, Los Angeles, CA 90095 USA

[8] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

MEDIATED GENE-EXPRESSION; FOCAL CEREBRAL-ISCHEMIA; EXPERIENCE-DEPENDENT PLASTICITY; DIRECT-CURRENT STIMULATION; MOTOR CORTEX; TONIC INHIBITION; NEURONS; EXCITABILITY; BRAIN; ACTIVATION;

D O I：

10.1038/s41467-018-04445-9

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：

Treatments that stimulate neuronal excitability enhance motor performance after stroke. cAMP-response-element binding protein (CREB) is a transcription factor that plays a key role in neuronal excitability. Increasing the levels of CREB with a viral vector in a small pool of motor neurons enhances motor recovery after stroke, while blocking CREB signaling prevents stroke recovery. Silencing CREB-transfected neurons in the peri-infarct region with the hM4Di-DREADD blocks motor recovery. Reversing this inhibition allows recovery to continue, demonstrating that by manipulating the activity of CREB-transfected neurons it is possible to turn off and on stroke recovery. CREB transfection enhances remapping of injured somatosensory and motor circuits, and induces the formation of new connections within these circuits. CREB is a central molecular node in the circuit responses after stroke that lead to recovery from motor deficits.

引用

页数：16

共 56 条

[1] Barth AL, 2000, J NEUROSCI, V20, P4206
[2] Neocortical movement representations are reduced and reorganized following bilateral intrastriatal 6-hydroxydopamine infusion and dopamine type-2 receptor antagonism
Brown, Andrew R.
Hu, Bin
Antle, Michael C.
Teskey, G. Campbell
[J]. EXPERIMENTAL NEUROLOGY, 2009, 220 (01) : 162 - 170
[3] In Vivo Voltage-Sensitive Dye Imaging in Adult Mice Reveals That Somatosensory Maps Lost to Stroke Are Replaced over Weeks by New Structural and Functional Circuits with Prolonged Modes of Activation within Both the Peri-Infarct Zone and Distant Sites
Brown, Craig E.
Aminoltejari, Khatereh
Erb, Heidi
Winship, Ian R.
Murphy, Timothy H.
[J]. JOURNAL OF NEUROSCIENCE, 2009, 29 (06) : 1719 - 1734
[4] Motor Learning Consolidates Arc-Expressing Neuronal Ensembles in Secondary Motor Cortex
Cao, Vania Yu
Ye, Yizhou
Mastwal, Surjeet
Ren, Ming
Coon, Matthew
Liu, Qing
Costa, Rui M.
Wang, Kuan Hong
[J]. NEURON, 2015, 86 (06) : 1385 - 1392
[5] Emergent Properties of Neural Repair: Elemental Biology to Therapeutic Concepts
Carmichael, S. Thomas
[J]. ANNALS OF NEUROLOGY, 2016, 79 (06) : 895 - 906
[6] Combined ampakine and BDNF treatments enhance poststroke functional recovery in aged mice via AKT-CREB signaling
Clarkson, Andrew N.
Parker, Kim
Nilsson, Michael
Walker, F. Rohan
Gowing, Emma K.
[J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2015, 35 (08) : 1272 - 1279
[7] Multimodal examination of structural and functional remapping in the mouse photothrombotic stroke model
Clarkson, Andrew N.
Lopez-Valdes, Hector E.
Overman, Justine J.
Charles, Andrew C.
Brennan, K. C.
Carmichael, S. Thomas
[J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2013, 33 (05) : 716 - 723
[8] AMPA Receptor-Induced Local Brain-Derived Neurotrophic Factor Signaling Mediates Motor Recovery after Stroke
Clarkson, Andrew N.
Overman, Justine J.
Zhong, Sheng
Mueller, Rudolf
Lynch, Gary
Carmichael, S. Thomas
[J]. JOURNAL OF NEUROSCIENCE, 2011, 31 (10) : 3766 - 3775
[9] Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke
Clarkson, Andrew N.
Huang, Ben S.
MacIsaac, Sarah E.
Mody, Istvan
Carmichael, S. Thomas
[J]. NATURE, 2010, 468 (7321) : 305 - U193
[10] Repairing the human brain after stroke: I. Mechanisms of spontaneous recovery
Cramer, Steven C.
[J]. ANNALS OF NEUROLOGY, 2008, 63 (03) : 272 - 287

← 1 2 3 4 5 6 →