New insights on synaptic dysfunction in neuropsychiatric disorders

被引:44
作者
Caldeira, Gladys Lima [1 ,2 ]
Peca, Joao [1 ,2 ]
Carvalho, Ana Luisa [1 ,3 ]
机构
[1] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, P-3004504 Coimbra, Portugal
[2] Univ Coimbra, IIIUC Interdisciplinary Res Inst, P-3030789 Coimbra, Portugal
[3] Univ Coimbra, Dept Life Sci, P-3004517 Coimbra, Portugal
关键词
3 PYRAMIDAL CELLS; STRUCTURAL PLASTICITY; DENDRITIC MORPHOLOGY; ALTERED EXPRESSION; AUTISM; MICRODELETION; MICE; PHENOTYPES; MUTATIONS; SPINES;
D O I
10.1016/j.conb.2019.01.004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Growing evidence implicates synaptic proteins in the pathogenesis of neuropsychiatric disorders such as autism spectrum disorder (ASD), intellectual disability (ID) and schizophrenia. In fact, mutations in genes encoding synaptic proteins are enriched and overlap among different conditions highlighting the complex and pleiotropic nature of these disorders. In this review, we discuss recently described candidate genes that affect excitatory synapse function and result in changes in spine number and morphology. Spine pathology has been observed in several animal models of disease and in human brain post-mortem samples from ID, ASD, and schizophrenia patients. Recent data point to convergent mechanisms, such as dysregulation of the actin cytoskeleton and dysfunction of microglia synaptic remodeling, underlying dendritic spine dysgenesis. Interestingly, the reversion of important pathologic features, including spine abnormalities, has been observed in adult animal models of neuropsychiatric disorders, suggesting that therapies may not be restricted to a specific developmental window. Shedding light on the specific mechanisms impacted in neuropsychiatric disorders will undeniably contribute to the development of more directed and personalized therapies.
引用
收藏
页码:62 / 70
页数:9
相关论文
共 64 条
[1]   Analysis of shared heritability in common disorders of the brain [J].
Anttila, Verneri ;
Bulik-Sullivan, Brendan ;
Finucane, Hilary K. ;
Walters, Raymond K. ;
Bras, Jose ;
Duncan, Laramie ;
Escott-Price, Valentina ;
Falcone, Guido J. ;
Gormley, Padhraig ;
Malik, Rainer ;
Patsopoulos, Nikolaos A. ;
Ripke, Stephan ;
Wei, Zhi ;
Yu, Dongmei ;
Lee, Phil H. ;
Turley, Patrick ;
Grenier-Boley, Benjamin ;
Chouraki, Vincent ;
Kamatani, Yoichiro ;
Berr, Claudine ;
Letenneur, Luc ;
Hannequin, Didier ;
Amouyel, Philippe ;
Boland, Anne ;
Deleuze, Jean-Francois ;
Duron, Emmanuelle ;
Vardarajan, Badri N. ;
Reitz, Christiane ;
Goate, Alison M. ;
Huentelman, Matthew J. ;
Kamboh, M. Ilyas ;
Larson, Eric B. ;
Rogaeva, Ekaterina ;
St George-Hyslop, Peter ;
Hakonarson, Hakon ;
Kukull, Walter A. ;
Farrer, Lindsay A. ;
Barnes, Lisa L. ;
Beach, Thomas G. ;
Demirci, F. Yesim ;
Head, Elizabeth ;
Hulette, Christine M. ;
Jicha, Gregory A. ;
Kauwe, John S. K. ;
Kaye, Jeffrey A. ;
Leverenz, James B. ;
Levey, Allan I. ;
Lieberman, Andrew P. ;
Pankratz, Vernon S. ;
Poon, Wayne W. .
SCIENCE, 2018, 360 (6395) :1313-+
[2]   Rapid Dispersion of SynGAP from Synaptic Spines Triggers AMPA Receptor Insertion and Spine Enlargement during LTP [J].
Araki, Yoichi ;
Zeng, Menglong ;
Zhang, Mingjie ;
Huganir, Richard L. .
NEURON, 2015, 85 (01) :173-189
[3]   Actin polymerization is reduced in the anterior cingulate cortex of elderly patients with schizophrenia [J].
Bhambhvani, Hriday P. ;
Mueller, Toni M. ;
Simmons, Micah S. ;
Meador-Woodruff, James H. .
TRANSLATIONAL PSYCHIATRY, 2017, 7
[4]   Decreased expression of cortactin in the schizophrenia brain [J].
Bhambhvani, Hriday P. ;
Simmons, Micah ;
Haroutunian, Vahram ;
Meador-Woodruff, James H. .
NEUROREPORT, 2016, 27 (03) :145-150
[5]   Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia [J].
Brennand, K. ;
Savas, J. N. ;
Kim, Y. ;
Tran, N. ;
Simone, A. ;
Hashimoto-Torii, K. ;
Beaumont, K. G. ;
Kim, H. J. ;
Topol, A. ;
Ladran, I. ;
Abdelrahim, M. ;
Matikainen-Ankney, B. ;
Chao, S-H ;
Mrksich, M. ;
Rakic, P. ;
Fang, G. ;
Zhang, B. ;
Yates, J. R., III ;
Gage, F. H. .
MOLECULAR PSYCHIATRY, 2015, 20 (03) :361-368
[6]   Structural plasticity upon learning: regulation and functions [J].
Caroni, Pico ;
Donato, Flavio ;
Muller, Dominique .
NATURE REVIEWS NEUROSCIENCE, 2012, 13 (07) :478-490
[7]   The Abl/Arg substrate ArgBP2/nArgBP2 coordinates the function of multiple regulatory mechanisms converging on the actin cytoskeleton [J].
Cestra, G ;
Toomre, D ;
Chang, S ;
De Camilli, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (05) :1731-1736
[8]   Altered Expression of ARP2/3 Complex Signaling Pathway Genes in Prefrontal Layer 3 Pyramidal Cells in Schizophrenia [J].
Datta, Dibyadeep ;
Arion, Dominique ;
Roman, Kaitlyn M. ;
Volk, David W. ;
Lewis, David A. .
AMERICAN JOURNAL OF PSYCHIATRY, 2017, 174 (02) :163-171
[9]   Altered Expression of CDC42 Signaling Pathway Components in Cortical Layer 3 Pyramidal Cells in Schizophrenia [J].
Datta, Dibyadeep ;
Arion, Dominique ;
Corradi, John P. ;
Lewis, David A. .
BIOLOGICAL PSYCHIATRY, 2015, 78 (11) :775-785
[10]   SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism [J].
Durand, C. M. ;
Perroy, J. ;
Loll, F. ;
Perrais, D. ;
Fagni, L. ;
Bourgeron, T. ;
Montcouquiol, M. ;
Sans, N. .
MOLECULAR PSYCHIATRY, 2012, 17 (01) :71-84