Browsing by Author "Sun, Zheng"

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    Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection
    (Springer Nature, 2019-02) Zhou, Wenjun; He, Yanlin; Rehman, Atteeq U.; Kong, Yan; Hong, Sungguan; Ding, Guolian; Yalamanchili, Hari Krishna; Wan, Ying-Wooi; Paul, Basil; Wang, Chuhan; Gong, Yingyun; Zhou, Wenxian; Liu, Hao; Dean, John; Scalais, Emmanuel; O’Driscoll, Mary; Morton, Jenny E.V.; Hou, Xinguo; Wu, Qi; Tong, Qingchun; Liu, Zhandong; Liu, Pengfei; Xu, Yong; Sun, Zheng; Biostatistics, IU School of Medicine
    Nuclear receptor corepressor 1 (NCOR1) and NCOR2 (also known as SMRT) regulate gene expression by activating histone deacetylase 3 through their deacetylase activation domain (DAD). We show that mice with DAD knock-in mutations have memory deficits, reduced anxiety levels, and reduced social interactions. Mice with NCOR1 and NORC2 depletion specifically in GABAergic neurons (NS-V mice) recapitulated the memory deficits and had reduced GABAA receptor subunit α2 (GABRA2) expression in lateral hypothalamus GABAergic (LHGABA) neurons. This was associated with LHGABA neuron hyperexcitability and impaired hippocampal long-term potentiation, through a monosynaptic LHGABA to CA3GABA projection. Optogenetic activation of this projection caused memory deficits, whereas targeted manipulation of LHGABA or CA3GABA neuron activity reversed memory deficits in NS-V mice. We describe de novo variants in NCOR1, NCOR2 or HDAC3 in patients with intellectual disability or neurodevelopmental disorders. These findings identify a hypothalamus-hippocampus projection that may link endocrine signals with synaptic plasticity through NCOR-mediated regulation of GABA signaling.
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    Retrospective assessment of at-risk myocardium in reperfused acute myocardial infarction patients using contrast‐enhanced balanced steady‐state free‐precession cardiovascular magnetic resonance at 3T with SPECT validation
    (Elsevier, 2021-03-15) Sun, Zheng; Zhang, Qiuhang; Zhao, Huan; Yan, Chengxi; Yang, Hsin‑Jung; Li, Debiao; Li, Kuncheng; Liu, Zhi; Yang, Qi; Dharmakumar, Rohan; Medicine, School of Medicine
    Background: Contrast-enhanced (CE) steady-state free precession (SSFP) CMR at 1.5T has been shown to be a valuable alternative to T2-based methods for the detection and quantifications of area-at-risk (AAR) in acute myocardial infarction (AMI) patients. However, CE-SSFP's capacity for assessment of AAR at 3T has not been investigated. We examined the clinical utility of CE-SSFP and T2-STIR for the retrospective assessment of AAR at 3T with single-photon-emission-computed tomography (SPECT) validation. Materials and methods: A total of 60 AMI patients (ST-elevation AMI, n = 44; non-ST-elevation AMI, n = 16) were recruited into the CMR study between 3 and 7 days post revascularization. All patients underwent T2-STIR, CE-bSSFP and late-gadolinium-enhancement CMR. For validation, SPECT images were acquired in a subgroup of patients (n = 30). Results: In 53 of 60 patients (88 %), T2-STIR was of diagnostic quality compared with 54 of 60 (90 %) with CE-SSFP. In a head-to-head per-slice comparison (n = 365), there was no difference in AAR quantified using T2-STIR and CE-SSFP (R2 = 0.92, p < 0.001; bias:-0.4 ± 0.8 cm2, p = 0.46). On a per-patient basis, there was good agreement between CE-SSFP (n = 29) and SPECT (R2 = 0.86, p < 0.001; bias: - 1.3 ± 7.8 %LV, p = 0.39) for AAR determination. T2-STIR also showed good agreement with SPECT for AAR measurement (R2 = 0.81, p < 0.001, bias: 0.5 ± 11.1 %LV, p = 0.81). There was also a strong agreement between CE-SSFP and T2-STIR with respect to the assessment of AAR on per-patient analysis (R2 = 0.84, p < 0.001, bias: - 2.1 ± 10.1 %LV, p = 0.31). Conclusions: At 3T, both CE-SSFP and T2-STIR can retrospectively quantify the at-risk myocardium with high accuracy.