Long-term ketamine administration causes Tau protein phosphorylation and Tau protein-dependent AMPA receptor reduction in the hippocampus of mice

Li, Yanning; Ding, Runtao; Ren, Xinghua; Wen, Gehua; Dong, Zhibin; Yao, Hui; Tan, Yaqing; Yu, Hao; Wang, Xiaolong; Zhan, Xiaoni; Yao, Jun; Lü, Yan; Zhang, Guohua; Wu, Xu

doi:10.1016/j.toxlet.2019.08.023

Cited by 21 publications

(19 citation statements)

References 37 publications

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“…Phosphorylated tau is generally sequestered in the soma of neurons, with small traces founded in the nucleus [5]. Similar to other microtubule-associated proteins, tau preserves microtubule stability and monitors intracellular trafficking [6]. However, in AD, the normal function of tau is interrupted, and a large amount of phosphorylated tau accumulates.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer’s disease

Gao¹,

Chu

Gong³

et al. 2020

J Nanobiotechnol

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Background: Although many therapeutic strategies for Alzheimer's disease (AD) have been explored, these strategies are seldom used in the clinic. Therefore, AD therapeutic research is still urgently needed. One major challenge in the field of nanotherapeutics is to increase the selective delivery of drugs to a targeted location. Herein, we devised and tested a strategy for delivery of nanoparticles to neurons to inhibit tau aggregation by directly targeting p-tau. Results: Curcumin (CUR) is loaded onto red blood cell (RBC) membrane-coated PLGA particles bearing T807 molecules attached to the RBC membrane surface (T807/RPCNP). With the advantage of the suitable physicochemical properties of the PLGA nanoparticles and the unique biological functions of the RBC membrane, the RPCNP are stabilized and promote sustained CUR release, which provided improved biocompatibility and resulted in long-term presence in the circulation. Under the synergistic effects of T807, T807/RPCNP can not only effectively penetrate the blood-brain barrier (BBB), but they also possess high binding affinity to hyperphosphorylated tau in nerve cells where they inhibit multiple key pathways in tau-associated AD pathogenesis. When CUR was encapsulated, our data also demonstrated that CUR-loaded T807/RPCNP NPs can relieve AD symptoms by reducing p-tau levels and suppressing neuronal-like cells death both in vitro and in vivo. The memory impairment observed in an AD mouse model is significantly improved following systemic administration of CUR-loaded T807/RPCNP NPs. Conclusion: Intravenous neuronal tau-targeted T807-modified novel biomimetic nanosystems are a promising clinical candidate for the treatment of AD.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer’s disease

Gao¹,

Chu

Gong³

et al. 2020

J Nanobiotechnol

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“…Abnormal MCTs expression is involved in neurodegenerative disorders (Lee et al, 2012;Hong et al, 2019). Ketamine and other addictive drug abuse may lead to neurodegeneration and neurotoxicity (Ikonomidou et al, 1999;Moszczynska and Callan, 2017;Li et al, 2019). Thereby, these researches indicated that changes in cerebral MCTs expressions may be relevant to neurotoxicity induced by ketamine abuse.…”

Section: Discussionmentioning

confidence: 99%

Redistribution of Monocarboxylate 1 and 4 in Hippocampus and Spatial Memory Impairment Induced by Long-term Ketamine Administration

Ding

Tan

et al. 2020

Front. Behav. Neurosci.

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The monocarboxylate transporters (MCTs) MCT1, MCT2, and MCT4 are essential components of the astrocyte-neuron lactate shuttle (ANLS), which is a fundamental element of brain energetics. Decreased expression of MCTs can induce cognitive dysfunction of the brain. In the present study, we established a mouse model of long-term ketamine administration by subjecting mice to a 6-month course of a daily intraperitoneal injection of ketamine. These mice demonstrated learning and memory deficits and a significant decline in MCT1 and MCT4 proteins in the hippocampal membrane fraction, while cytoplasmic MCT1 and MCT4 protein levels were significantly increased. In contrast, the levels of global MCT2 protein were significantly increased. Analysis of mRNA levels found no changes in MCT1/4 transcripts, although the expression of MCT2 mRNA was significantly increased. We suggest that redistribution of hippocampal MCT1 and MCT4, but not MCT2 up-regulation, may be related to learning and memory deficits induced by long-term ketamine administration.

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“…Studies focus on the neurotoxicity of high dosing ketamine administration and long-term ketamine abuse (41,42). However, ketamine served as proper rescue, pharmacotherapy and, also, adjuvant for neuropathic pain with promising application prospect (8).…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine versus ketamine in attenuating neuropathic pain through modulating STING/TBK pathway to modulate spinal ER-phagy in neuropathic pain model

Liu

Ding

Wang

et al. 2020

Preprint

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Background: Our previous studies suggested that stimulator of interferon genes (STING) level was altered in medial prefrontal cortex (mPFC) of spinal nerve ligation (SNL) rats. Methods:In this study, we investigated that whether dexmedetomidine and ketamine provide antianxiety and anti-nociceptive effects via modulating spinal STING/TBK pathway to alter ER-phagy in SNL rats. We evaluated the analgesia and antianxiety effects of ketamine and dexmedetomidine in SNL rats. 2'3'-cGAMP (STING pathway agonist) was administrated to investigate whether enhanced spinal STING pathway could reverse dexmedetomidine or ketamine treatment effects in SNL rats respectively. Analgesia effects were measured with mechanical withdrawal threshold (MWT) and antianxiety effect was measured with open field test (OFT). Proteins expression levels were evaluated by Western blotting. Distribution and cellular localization of STING pathway and ER stress were evaluated by confocal immunofluorescence.Results: SNL induced mechanical hypersensitivity and anxiety; STING pathway was involved in the modulation of ER stress and ER-phagy in SNL rats; Dexmedetomidine and ketamine provided analgesia and antianxiety effects in SNL rats; Dexmedetomidine and ketamine alleviated ER stress via inhibiting STING pathway to enhance ER-phagy in SNL rats. Conclusions:In all, both ketamine and dexmedetomidine provided antianxiety and anti-nociceptive effects through alleviating ER stress via inhibiting STING/TBK pathway to modulate spinal ER-phagy in SNL rats.

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Long-term ketamine administration causes Tau protein phosphorylation and Tau protein-dependent AMPA receptor reduction in the hippocampus of mice

Cited by 21 publications

References 37 publications

RETRACTED ARTICLE: Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer’s disease

RETRACTED ARTICLE: Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer’s disease

Redistribution of Monocarboxylate 1 and 4 in Hippocampus and Spatial Memory Impairment Induced by Long-term Ketamine Administration

Dexmedetomidine versus ketamine in attenuating neuropathic pain through modulating STING/TBK pathway to modulate spinal ER-phagy in neuropathic pain model

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