Hippocampal circAnk3 Deficiency Causes Anxiety-like Behaviors and Social Deficits by Regulating the miR-7080-3p/IQGAP1 Pathway in Mice

He, Yuman; Jiang, Linhong; Liu, Haxiaoyu; Bu, Qian; Kuang, Weihong; Zhao, Ying; Chen, Yaxing; Zhang, Ni; Xiao, Yuzhou; Li, Shu; Chen, Rong; Han, Shuang; Zhou, Yuanyi; Zhang, Jiamei; Wan, Xuemei; Xu, Rui; Wang, Shaomin; Zhang, Haoluo; Gu, Hui; Wei, Qingfan; Qin, Feng; Zhao, Yue; Li, Hongchun; Wang, Liang; Wang, Xiaojie; Wang, Yonghai; Dai, Yanping; Li, Min; Chen, Yuanyuan; Wang, Hongbo; Tian, Jingwei; Zhao, Yinglan; Cen, Xiaobo

doi:10.1016/j.biopsych.2023.10.017

Cited by 3 publications

(1 citation statement)

References 39 publications

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“…CircRNAs are emerging as crucial players in gene regulation, involved in numerous cellular processes, including regulating transcription of their host genes, sponging miRNAs and RNA binding proteins (RBPs), as well as in uencing translation [22,44]. The implications of circRNAs in the pathogenesis of neuropsychiatric diseases have been documented [37,[45][46][47], but their involvement in SUD remains poorly understood [20,[48][49][50]. CircHomer1, derived from exons 2-5 of the Homer1 longest transcript [28], is a neuronal-enriched circRNA that has been reported to play a role in a myriad of biological and behavioral functions, including methamphetamine-induced CPP preference [51], neuronal plasticity [23], cognitive exibility and regulating synaptic gene expression [28].…”

Section: Discussionmentioning

confidence: 99%

Prefrontal circHomer1 regulates synaptic and behavioral adaptations induced by psychostimulants

Shi,

Chen,

Zhang

et al. 2024

Preprint

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Substance use disorder (SUD) represents a substantial challenge in neuropsychiatric medicine, with the molecular mechanisms underlying its etiology remaining elusive. The molecular underpinnings of SUD suggest a pivotal role for circular RNAs (circRNAs) in its pathophysiology. Herein, we present a study on circHomer1, a circRNA enriched in neurons, which is abnormal expression upon cocaine exposure. Employing models of repeated cocaine exposure and conditioning place preference (CPP), alongside virus-mediated gene regulation techniques, we revealed the contributory function of circHomer1 in cocaine-induced rewarding effects and synaptic adaptations. We found a notably downregulation of circHomer1 expression in the prelimbic cortex consequent to repeated cocaine exposure in both rat model and patients with cocaine use disorder. Elevation of circHomer1 levels resulted in a pronounced attenuation of cocaine-induced CPP, whereas suppression of circHomer1 expression enhanced the rewarding effects. These outcomes were specifically observed in excitatory neurons, implicating a cell type-specific function of circHomer1. Furthermore, the restoration of circHomer1 rescued the reduction of mushroom-type dendritic spines and rectified deficits in the frequency of spontaneous excitatory postsynaptic currents associated with prolonged cocaine exposure. The modulatory actions of circHomer1 on cocaine-induced behavioral and synaptic responses were mediated by the dopamine receptor D1. Intriguingly, the effects of circHomer1 were selective to psychostimulant drugs, with no influence on food or opioid reward. Our findings highlight the significant role of circHomer1 in regulating psychostimulants reward and identify a novel molecular regulator of the actions of psychostimulants on the brain’s reward circuitry, providing a new strategy for treating drug addiction.

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Section: Discussionmentioning

confidence: 99%

Prefrontal circHomer1 regulates synaptic and behavioral adaptations induced by psychostimulants

Shi,

Chen,

Zhang

et al. 2024

Preprint

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Synthetic circRNA therapeutics: innovations, strategies, and future horizons

Cai,

Qiu,

Chi‐Shing Cho

et al. 2024

MedComm

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Small molecule drugs are increasingly emerging as innovative and effective treatments for various diseases, with mRNA therapeutics being a notable representative. The success of COVID‐19 vaccines has underscored the transformative potential of mRNA in RNA therapeutics. Within the RNA family, there is another unique type known as circRNA. This single‐stranded closed‐loop RNA molecule offers notable advantages over mRNA, including enhanced stability and prolonged protein expression, which may significantly impact therapeutic strategies. Furthermore, circRNA plays a pivotal role in the pathogenesis of various diseases, such as cancers, autoimmune disorders, and cardiovascular diseases, making it a promising clinical intervention target. Despite these benefits, the application of circRNA in clinical settings remains underexplored. This review provides a comprehensive overview of the current state of synthetic circRNA therapeutics, focusing on its synthesis, optimization, delivery, and diverse applications. It also addresses the challenges impeding the advancement of circRNA therapeutics from bench to bedside. By summarizing these aspects, the review aims to equip researchers with insights into the ongoing developments and future directions in circRNA therapeutics. Highlighting both the progress and the existing gaps in circRNA research, this review offers valuable perspectives for advancing the field and guiding future investigations.

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Anxiety disorders: Treatments, models, and circuitry mechanisms

Ren,

Fan,

et al. 2024

European Journal of Pharmacology

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Hippocampal circAnk3 Deficiency Causes Anxiety-like Behaviors and Social Deficits by Regulating the miR-7080-3p/IQGAP1 Pathway in Mice

Cited by 3 publications

References 39 publications

Prefrontal circHomer1 regulates synaptic and behavioral adaptations induced by psychostimulants

Prefrontal circHomer1 regulates synaptic and behavioral adaptations induced by psychostimulants

Synthetic circRNA therapeutics: innovations, strategies, and future horizons

Anxiety disorders: Treatments, models, and circuitry mechanisms

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