References (5)

Title : NMDA receptor hypofunction underlies deficits in parvalbumin interneurons and social behavior in neuroligin 3 R451C knockin mice - Cao_2022_Cell.Rep_41_111771
Author(s) : Cao W , Li JH , Lin S , Xia QQ , Du YL , Yang Q , Ye YZ , Zeng LH , Li XY , Xu J , Luo JH
Ref : Cell Rep , 41 :111771 , 2022
Abstract : Neuroligins (NLs), a family of postsynaptic cell-adhesion molecules, have been associated with autism spectrum disorder. We have reported that dysfunction of the medial prefrontal cortex (mPFC) leads to social deficits in an NL3 R451C knockin (KI) mouse model of autism. However, the underlying molecular mechanism remains unclear. Here, we find that N-methyl-D-aspartate receptor (NMDAR) function and parvalbumin-positive (PV+) interneuron number and expression are reduced in the mPFC of the KI mice. Selective knockdown of NMDAR subunit GluN1 in the mPFC PV+ interneuron decreases its intrinsic excitability. Restoring NMDAR function by its partial agonist D-cycloserine rescues the PV+ interneuron dysfunction and social deficits in the KI mice. Interestingly, early D-cycloserine administration at adolescence prevents adult KI mice from social deficits. Together, our results suggest that NMDAR hypofunction and the resultant PV+ interneuron dysfunction in the mPFC may constitute a central node in the pathogenesis of social deficits in the KI mice.
ESTHER : Cao_2022_Cell.Rep_41_111771
PubMedSearch : Cao_2022_Cell.Rep_41_111771
PubMedID: 36476879

Title : Neuroligin 3 Regulates Dendritic Outgrowth by Modulating Akt\/mTOR Signaling - Xu_2019_Front.Cell.Neurosci_13_518
Author(s) : Xu J , Du YL , Xu JW , Hu XG , Gu LF , Li XM , Hu PH , Liao TL , Xia QQ , Sun Q , Shi L , Luo JH , Xia J , Wang Z
Ref : Front Cell Neurosci , 13 :518 , 2019
Abstract : Neuroligins (NLs) are a group of postsynaptic cell adhesion molecules that function in synaptogenesis and synaptic transmission. Genetic defects in neuroligin 3 (NL3), a member of the NL protein family, are associated with autism. Studies in rodents have revealed that mutations of NL3 gene lead to increased growth and complexity in dendrites in the central nervous system. However, the detailed mechanism is still unclear. In our study, we found that deficiency of NL3 led to morphological changes of the pyramidal neurons in layer II/III somatosensory cortex in mice, including enlarged somata, elongated dendritic length, and increased dendritic complexity. Knockdown of NL3 in cultured rat neurons upregulated Akt/mTOR signaling, resulting in both increased protein synthesis and dendritic growth. Treating neurons with either rapamycin to inhibit the mTOR or LY294002 to inhibit the PI3K/Akt activity rescued the morphological abnormalities resulting from either NL3 knockdown or knockout (KO). In addition, we found that the hyperactivated Akt/mTOR signaling associated with NL3 defects was mediated by a reduction in phosphatase and tensin (PTEN) expression, and that MAGI-2, a scaffold protein, interacted with both NL3 and PTEN and could be a linker between NL3 and Akt/mTOR signaling pathway. In conclusion, our results suggest that NL3 regulates neuronal morphology, especially dendritic outgrowth, by modulating the PTEN/Akt/mTOR signaling pathway, probably via MAGI-2. Thereby, this study provides a new link between NL3 and neuronal morphology.
ESTHER : Xu_2019_Front.Cell.Neurosci_13_518
PubMedSearch : Xu_2019_Front.Cell.Neurosci_13_518
PubMedID: 31849609

Title : Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice - Cao_2018_Neuron_97_1253
Author(s) : Cao W , Lin S , Xia QQ , Du YL , Yang Q , Zhang MY , Lu YQ , Xu J , Duan SM , Xia J , Feng G , Luo JH
Ref : Neuron , 97 :1253 , 2018
Abstract : Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits. However, neither the brain regions involved in social novelty nor the underlying mechanisms are clearly understood. Here, we found decreased excitability of fast-spiking interneurons and dysfunction of gamma oscillation in the medial prefrontal cortex (mPFC), which contributed to the social novelty deficit in the KI mice. Neuronal firing rates and phase-coding abnormalities were also detected in the KI mice during social interactions. Interestingly, optogenetic stimulation of parvalbumin interneurons in the mPFC at 40 Hz nested at 8 Hz positively modulated the social behaviors of mice and rescued the social novelty deficit in the KI mice. Our findings suggest that gamma oscillation dysfunction in the mPFC leads to social deficits in autism, and manipulating mPFC PV interneurons may reverse the deficits in adulthood.
ESTHER : Cao_2018_Neuron_97_1253
PubMedSearch : Cao_2018_Neuron_97_1253
PubMedID: 29503190
Gene_locus related to this paper: mouse-3neur

Title : [Association of hepatic lipase gene promoter polymorphism -514C\/T with nonalcoholic fatty liver disease] - Zhan_2008_Zhonghua.Gan.Zang.Bing.Za.Zhi_16_375
Author(s) : Zhan Q , Li YY , Nie YQ , Zhou YJ , Du YL , Sha WH , Wang H
Ref : Zhonghua Gan Zang Bing Za Zhi , 16 :375 , 2008
Abstract : OBJECTIVE: To study the prevalence of the hepatic lipase gene (LIPC) promoter polymorphism (at position -514) in patients with nonalcoholic fatty liver disease (NAFLD), and its relationship with the susceptibility to NAFLD.
METHODS: Genotype of LIPC promoter was detected with PCR-RFLP in 106 patients with NAFLD. Body mass index, waist-to-hip ratio (WHR), blood pressure, CHOL, HDL, LDL, TG, FPG and FINS of the patients were measured. Index of insulin resistance was determined using the homeostasis model assessment (HOMA) method. One hundred six healthy subjects matched for age and sex served as controls.
RESULTS: The frequency of CC genotype and C allele in the NAFLD group were significantly higher than those in the control group (31.1% vs 26.4%, 62.7% vs 54.2%, P<0.05). Compared with TT genotype, both CC genotype and CT genotypes had higher relative risk of NAFLD (OR: 3.73, 95% CI: 1.31, 10.63; OR: 3.60, 95% CI: 1.35, 9.60). At the same time, the non-carriers of T allele in -514 had higher WHR than the T carriers (0.877+/-0.06 vs 0.848+/-0.06, t=2.072, P<0.05)). Logistic regression analysis showed that T substitution in LIPC-514 position (OR: 1.28, 95% CI 0.10-0.74) had a lower susceptibility to NAFLD. CONCLUSION: The LIPC-514C/T polymorphism is associated with WHR, and the T substitution of LIPC-514 may lower the susceptibility to NAFLD.
ESTHER : Zhan_2008_Zhonghua.Gan.Zang.Bing.Za.Zhi_16_375
PubMedSearch : Zhan_2008_Zhonghua.Gan.Zang.Bing.Za.Zhi_16_375
PubMedID: 18510853
Gene_locus related to this paper: human-LIPC

Title : Genome-wide ORFeome cloning and analysis of Arabidopsis transcription factor genes - Gong_2004_Plant.Physiol_135_773
Author(s) : Gong W , Shen YP , Ma LG , Pan Y , Du YL , Wang DH , Yang JY , Hu LD , Liu XF , Dong CX , Ma L , Chen YH , Yang XY , Gao Y , Zhu D , Tan X , Mu JY , Zhang DB , Liu YL , Dinesh-Kumar SP , Li Y , Wang XP , Gu HY , Qu LJ , Bai SN , Lu YT , Li JY , Zhao JD , Zuo J , Huang H , Deng XW , Zhu YX
Ref : Plant Physiol , 135 :773 , 2004
Abstract : Here, we report our effort in generating an ORFeome collection for the Arabidopsis transcription factor (TF) genes. In total, ORFeome clones representing 1,282 Arabidopsis TF genes have been obtained in the Gateway high throughput cloning pENTR vector, including 411 genes whose annotation lack cDNA support. All the ORFeome inserts have also been mobilized into a yeast expression destination vector, with an estimated 85% rate of expressing the respective proteins. Sequence analysis of these clones revealed that 34 of them did not match with either the reported cDNAs or current predicted open-reading-frame sequences. Among those, novel alternative splicing of TF gene transcripts is responsible for the observed differences in at least five genes. However, those alternative splicing events do not appear to be differentially regulated among distinct Arabidopsis tissues examined. Lastly, expression of those TF genes in 17 distinct Arabidopsis organ types and the cultured cells was profiled using a 70-mer oligo microarray.
ESTHER : Gong_2004_Plant.Physiol_135_773
PubMedSearch : Gong_2004_Plant.Physiol_135_773
PubMedID: 15208423
Gene_locus related to this paper: arath-Q9FN74