首页 | 本学科首页   官方微博 | 高级检索  
检索        


Impaired synaptic development in a maternal immune activation mouse model of neurodevelopmental disorders
Institution:1. Pediatrics and Neuroscience, Harvard Medical School, Lurie Center for Autism, Massachusetts General Hospital for Children, Boston, MA 02126, United States;2. Psychology and Neuroscience, Duke University, Durham, NC 27708, United States;3. Pediatrics and Anatomy/Neurobiology, University of California-Irvine, Irvine, CA 92697, United States;1. Department of Pediatrics, David Geffen School of Medicine at UCLA, USA;2. Department of Neurology, David Geffen School of Medicine at UCLA, USA;3. UCLA Children''s Discovery and Innovation Institute, USA;1. Department of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;2. Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands;3. FrieslandCampina, Amersfoort, The Netherlands
Abstract:Both genetic and environmental factors are thought to contribute to neurodevelopmental and neuropsychiatric disorders with maternal immune activation (MIA) being a risk factor for both autism spectrum disorders and schizophrenia. Although MIA mouse offspring exhibit behavioral impairments, the synaptic alterations in vivo that mediate these behaviors are not known. Here we employed in vivo multiphoton imaging to determine that in the cortex of young MIA offspring there is a reduction in number and turnover rates of dendritic spines, sites of majority of excitatory synaptic inputs. Significantly, spine impairments persisted into adulthood and correlated with increased repetitive behavior, an ASD relevant behavioral phenotype. Structural analysis of synaptic inputs revealed a reorganization of presynaptic inputs with a larger proportion of spines being contacted by both excitatory and inhibitory presynaptic terminals. These structural impairments were accompanied by altered excitatory and inhibitory synaptic transmission. Finally, we report that a postnatal treatment of MIA offspring with the anti-inflammatory drug ibudilast, prevented both synaptic and behavioral impairments. Our results suggest that a possible altered inflammatory state associated with maternal immune activation results in impaired synaptic development that persists into adulthood but which can be prevented with early anti-inflammatory treatment.
Keywords:Autism  Dendritic spines  Excitation  Inhibition  Inflammation  Anti-inflammatory
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号