Tlr7 deletion alters expression profiles of genes related to neural function and regulates mouse behaviors and contextual memory

被引:27
|
作者
Hung, Yun-Fen [1 ,2 ,3 ]
Chen, Chiung-Ya [3 ]
Li, Wan-Chen [3 ,4 ,5 ]
Wang, Ting-Fang [3 ,4 ,5 ]
Hsueh, Yi-Ping [3 ,4 ,5 ]
机构
[1] Natl Yang Ming Univ, Dept Life Sci, Taipei 112, Taiwan
[2] Natl Yang Ming Univ, Inst Genome Sci, Taipei 112, Taiwan
[3] Acad Sinica, Inst Mol Biol, 128 Acad Rd,Sect 2, Taipei 115, Taiwan
[4] Acad Sinica, Inst Mol Biol, Taiwan Int Grad Program Mol & Cellular Biol, Taipei 115, Taiwan
[5] Natl Def Med Ctr, Inst Life Sci, Taipei 115, Taiwan
关键词
Aggression; Anxiety; Contextual fear memory; Next generation sequencing; Toll-like receptor; Transcriptomic profiling; TOLL-LIKE RECEPTOR; NEURONAL MORPHOLOGY; MICE; RECOGNITION; DROSOPHILA; PROTEIN; MODEL; NEURODEGENERATION; INFECTION; IMMUNITY;
D O I
10.1016/j.bbi.2018.06.006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The neuronal innate immune system recognizes endogenous danger signals and regulates neuronal development and function. Toll-like receptor 7 (TLR7), one of the TLRs that trigger innate immune responses in neurons, controls neuronal morphology. To further assess the function of TLR7 in the brain, we applied next generation sequencing to investigate the effect of Tlr7 deletion on gene expression in hippocampal and cortical mixed cultures and on mouse behaviors. Since previous in vivo study suggested that TLR7 is more critical for neuronal morphology at earlier developmental stages, we analyzed two time-points (4 and 18 DIV) to represent young and mature neurons, respectively. At 4 DIV, Tlr7 KO neurons exhibited reduced expression of genes involved in neuronal development, synaptic organization and activity and behaviors. Some of these Tlr7-regulated genes are also associated with multiple neurological and neuropsychiatric diseases. TLR7-regulated transcriptomic profiles differed at 18 DIV. Apart from neuronal genes, genes related to glial cell development and differentiation became sensitive to Tlr7 deletion at 18 DIV. Moreover, Tlr7 KO mice exhibited altered behaviors in terms of anxiety, aggression, olfaction and contextual fear memory. Electrophysiological analysis further showed an impairment of long-term potentiation in Tlr7 KO hippocampus. Taken together, these results indicate that TLR7 regulates neural development and brain function, even in the absence of infectious or pathogenic molecules. Our findings strengthen evidence for the role of the neuronal innate immune system in fine-tuning neuronal morphology and activity and implicate it in neuropsychiatric disorders.
引用
收藏
页码:101 / 113
页数:13
相关论文
共 5 条
  • [1] TLR7/8 Differentially Regulates Fcγ Receptor Expression and Function
    Butchar, Jonathan P.
    Mehta, Payal
    Justiniano, Steven E.
    Guenterberg, Kristan D.
    Kanneganti, Thirumala-Devi
    Amer, Amal
    Muthusamy, Natarajan
    Jarjoura, David
    Marsh, Clay B.
    Carson, William E., III
    Byrd, John C.
    Tridandapani, Susheela
    BLOOD, 2009, 114 (22) : 1391 - 1392
  • [2] Perinatal α-linolenic acid availability alters the expression of genes related to memory and to epigenetic machinery, and the Mecp2 DNA methylation in the whole brain of mouse offspring
    He, Fuli
    Lupu, Daniel S.
    Niculescu, Mihai D.
    INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 2014, 36 : 38 - 44
  • [3] Deletion of P2X7 receptor causes genome-wide alterations of genes expression including genes related to depression in mouse amygdale - a whole genome microarray study
    Csolle, C.
    Sperlagh, B.
    ACTA PHYSIOLOGICA HUNGARICA, 2010, 97 (04) : 432 - 432
  • [4] Deletion of P2X7 receptor causes genome-wide alterations of genes expression including genes related to depression in mouse amygdale-a whole genome microarray study
    Csoelle, Cecilia Katalin
    Spcrlagh, Bcata
    PURINERGIC SIGNALLING, 2010, 6 : 47 - 48
  • [5] Overexpression of the IGF-II/M6P Receptor in Mouse Fibroblast Cell Lines Differentially Alters Expression Profiles of Genes Involved in Alzheimer's Disease-Related Pathology
    Wang, Yanlin
    Thinakaran, Gopal
    Kar, Satyabrata
    PLOS ONE, 2014, 9 (05):