Neuronal <scp>HMGB1</scp> in nucleus accumbens regulates cocaine reward memory

Gao, Shuang-Qi; Zhang, Hai; He, Jin-Gang; Zheng, Hongchen; Zhang, Pei-Wei; Xu, Junfeng; Shen, Zu-Cheng; Zhao, Huanhuan; Wang, Fang; Hu, Zhuang-Li; Chen, Jianguo

doi:10.1111/adb.12739

Cited by 12 publications

(13 citation statements)

References 48 publications

(62 reference statements)

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“…Normally, HMGB1 is mainly located in the nucleus and binds to chromatin, but it can shuttle from the nucleus to the cytoplasm under various stress conditions and then into the extracellular space, for example, when induced by elevated reactive oxygen species (ROS) production during porcine circovirus type 2 infection 8 , 9 . The subcellular location of HMGB1 varies depending on cell type, tissue, and stress signals, and its location is key to its functions 10 , 11 . HMG proteins have multiple nuclear functions, and additional extracellular and proinflammatory activities are continuously being discovered for HMGB1 5 , 12 and related proteins, such as HMGB2 13 and HMGN1 14 .…”

Section: Introductionmentioning

confidence: 99%

The mechanism of HMGB1 secretion and release

2022

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High mobility group box 1 (HMGB1) is a nonhistone nuclear protein that has multiple functions according to its subcellular location. In the nucleus, HMGB1 is a DNA chaperone that maintains the structure and function of chromosomes. In the cytoplasm, HMGB1 can promote autophagy by binding to BECN1 protein. After its active secretion or passive release, extracellular HMGB1 usually acts as a damage-associated molecular pattern (DAMP) molecule, regulating inflammation and immune responses through different receptors or direct uptake. The secretion and release of HMGB1 is fine-tuned by a variety of factors, including its posttranslational modification (e.g., acetylation, ADP-ribosylation, phosphorylation, and methylation) and the molecular machinery of cell death (e.g., apoptosis, pyroptosis, necroptosis, alkaliptosis, and ferroptosis). In this minireview, we introduce the basic structure and function of HMGB1 and focus on the regulatory mechanism of HMGB1 secretion and release. Understanding these topics may help us develop new HMGB1-targeted drugs for various conditions, especially inflammatory diseases and tissue damage.

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Section: Introductionmentioning

confidence: 99%

The mechanism of HMGB1 secretion and release

2022

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“…Consequently, cocaine-TLR4, but not HMGB1-TLR4, contributes to the formation of cocaine-associated memory in the NAc (Figure 6). Tracey, 2011;Harris et al, 2012;Mao et al, 2022), which shows to be activated over 24 h after first cocaine injection (Gao et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

The HMGB1–RAGE axis in nucleus accumbens facilitates cocaine‐induced conditioned place preference via modulating microglial activation

Ye,

Gao,

Liu

et al. 2024

Brain and Behavior

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IntroductionRepeated exposure to cocaine induces microglial activation. Cocaine exposure also induces a release of high mobility group box‐1 (HMGB1) from neurons into the extracellular space in the nucleus accumbens (NAc). HMGB1 is an important late inflammatory mediator of microglial activation. However, whether the secretion of HMGB1 acts on microglia or contributes to cocaine addiction is largely unknown.MethodsRats were trained by intraperitoneal cocaine administration and cocaine‐induced conditioned place preference (CPP). Expression of HMGB1 was regulated by viral vectors. Activation of microglia was inhibited by minocycline. Interaction of HMGB1 and the receptor for advanced glycation end products (RAGE) was disrupted by peptide.ResultsCocaine injection facilitated HMGB1 signaling, together with the delayed activation of microglia concurrently in the NAc. Furthermore, the inhibition of HMGB1 or microglia activation attenuated cocaine‐induced CPP. Box A, a specific antagonist to interrupt the interaction of HMGB1 and RAGE, abolished the expression of cocaine reward memory. Meanwhile, the inhibition of HMGB1–RAGE interaction suppressed cocaine‐induced microglial activation, as well as the consolidation of cocaine‐induced memory.ConclusionAll above results suggest that the neural HMGB1 induces activation of microglia through RAGE, which contributes to the consolidation of cocaine reward memory. These findings offer HMGB1–RAGE axis as a new target for the treatment of drug addiction.

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“…Exposure to drugs such as methamphetamine, cocaine and ethanol activates neuroinflammatory pathways thatare associated withthe release of HMGB1-1 in the striatum and nucleus accumbens, as part of addictive behaviors and drug reward ( Alasmari et al, 2020 ; Gao et al, 2020 ). The overall similarity in inflammatory profiles and brain regions between drugs of abuse and that observed in this model of chronic JUUL exposure (inhalation for 3 months) raises concern as it suggests that e-cigarette use is associated with addictive behaviors ( Vogel et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice

Moshensky

Brand

Alhaddad

et al. 2022

eLife

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While health effects of conventional tobacco are well defined, data on vaping devices, including one of the most popular e-cigarettes which have high nicotine levels, are less established. Prior acute e-cigarette studies have demonstrated inflammatory and cardiopulmonary physiology changes while chronic studies have demonstrated extra-pulmonary effects, including neurotransmitter alterations in reward pathways. In this study we investigated the impact of inhalation of aerosols produced from pod-based, flavored e-cigarettes (JUUL) aerosols three times daily for 3 months on inflammatory markers in the brain, lung, heart, and colon. JUUL aerosol exposure induced upregulation of cytokine and chemokine gene expression and increased HMGB1 and RAGE in the nucleus accumbens in the central nervous system. Inflammatory gene expression increased in the colon, while gene expression was more broadly altered by e-cigarette aerosol inhalation in the lung. Cardiopulmonary inflammatory responses to acute lung injury with lipopolysaccharide were exacerbated in the heart. Flavor-specific findings were detected across these studies. Our findings suggest that daily e-cigarette use may cause neuroinflammation, which may contribute to behavioral changes and mood disorders. In addition, e-cigarette use may cause gut inflammation, which has been tied to poor systemic health, and cardiac inflammation, which leads to cardiovascular disease.

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Neuronal HMGB1 in nucleus accumbens regulates cocaine reward memory

Cited by 12 publications

References 48 publications

The mechanism of HMGB1 secretion and release

The mechanism of HMGB1 secretion and release

The HMGB1–RAGE axis in nucleus accumbens facilitates cocaine‐induced conditioned place preference via modulating microglial activation

Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice

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