Retigabine ameliorates acute stress-induced impairment of spatial memory retrieval through regulating USP2 signaling pathways in hippocampal CA1 area

Li, Cai; Zhang, Ji; Xu, Haiwei; Chang, Mujun; Lv, Chun-Tao; Xue, Wenhua; Song, Zhizhen; Zhang, Lizhen; Zhang, Xiaojian; Tian, Xin

doi:10.1016/j.neuropharm.2018.02.034

Cited by 19 publications

(16 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A significant improvement of studied parameters was observed on the second day of the experiment. It is known that people with alcohol use disorder suffer, apart from demonstrating other symptoms, also from disturbed spatial memory [20]. Hence, this effect of retigabine deserves special attention.…”

Section: Discussionmentioning

confidence: 99%

Beneficial effect of retigabine on memory in rats receiving ethanol

2020

View full text Add to dashboard Cite

Background Retigabine belongs to the novel generation of antiepileptic drugs but its complex mechanism of action causes that the drug might be effective in other diseases, for instance, alcohol dependence. It is known that ethanol abuse impaired the function of brain structures associated with memory and learning such as the hippocampus. In our previous study, retigabine reduced hippocampal changes induced by ethanol in the EEG rhythms in rabbits. This study is focused on the impact of retigabine on memory processes in male rats receiving alcohol. Methods Memory was evaluated in various experimental models: Morris water maze, Contextual, and Cued Fear Conditioning tests. Retigabine was administered for 3 weeks directly to the stomach via oral gavage at a dose of 10 mg/kg. Rats received also 20% ethanol (5 g/kg/day in two doses) via oral gavage for 3 weeks and had free access to 5% ethanol in the afternoon and at night. Morris water maze was performed after 1 and 3 weeks of ethanol administration and after 1 week from the discontinuation of ethanol administration. Contextual and Cued Fear Conditioning tests were carried out after 24 h and 72 h of alcohol discontinuation. Results The drug significantly decreased ethanol-induced memory disturbances during alcohol administration as well as slightly improved learning processes after the discontinuation of ethanol administration. Conclusions This beneficial effect of retigabine-ethanol interaction on memory may be a relevant element of the drug’s impact on the development of addiction.

show abstract

Section: Discussionmentioning

confidence: 99%

Beneficial effect of retigabine on memory in rats receiving ethanol

2020

View full text Add to dashboard Cite

show abstract

“…USP2 is abundantly expressed in neural cells in the intact mouse brain [120]. Correspondingly, an emerging body of evidence suggests significant roles for USP2 in the nervous system.…”

Section: Nervous Systemmentioning

confidence: 99%

“…In particular, stressinduced cognitive defects are attributable to the dysfunction of hippocampal channels or receptors [123,124]. Li et al reported that, in rats, acute stress led to cognitive failure, accompanied by the downregulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the hippocampal CA1 region [120], as well as significant decreases in the expression of PGC-1α, β-catenin, E4 promoter-binding protein 4 (E4BP4), and USP2. Because PGC1-α, β-catenin, and E4BP4 have been postulated as upstream regulators of USP2 [82], stress-induced attenuation of their expression may in turn attenuate hippocampal USP2.…”

Section: Nervous Systemmentioning

confidence: 99%

“…Because PGC1-α, β-catenin, and E4BP4 have been postulated as upstream regulators of USP2 [82], stress-induced attenuation of their expression may in turn attenuate hippocampal USP2. Retigabine, a drug that opens voltage-gated potassium channels, has been shown to abolish stress-induced cognitive defects; normalize the expression of PGC-1α, β-catenin, and USP2; and alleviate the increase in phosphorylated mammalian target of rapamycin (mTOR) and autophagy components [120]. Based on these findings, the authors speculated that USP2 deficiency impaired special memory retrieval via the aberrant expression of AMPA receptors and enhancement of mTOR-evoked autophagy [120].…”

Section: Nervous Systemmentioning

confidence: 99%

“…Although the modification of these factors may account for some of the USP2-elicted responses, it is presumed that not all USP2 targets have been discovered. For example, some reports indicate that USP2 potentially contributes to memory formation in the hippocampus and cerebral cortex [120]. The target of USP2 in this context has not yet been discerned, although mTOR and AMPA receptor 1 have been postulated [120].…”

Section: Perspectivesmentioning

confidence: 99%

See 2 more Smart Citations

USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes

Kitamura

Hashimoto

2021

IJMS

View full text Add to dashboard Cite

Ubiquitin specific protease (USP) 2 is a multifunctional deubiquitinating enzyme. USP2 modulates cell cycle progression, and therefore carcinogenesis, via the deubiquitination of cyclins and Aurora-A. Other tumorigenic molecules, including epidermal growth factor and fatty acid synthase, are also targets for USP2. USP2 additionally prevents p53 signaling. On the other hand, USP2 functions as a key component of the CLOCK/BMAL1 complex and participates in rhythmic gene expression in the suprachiasmatic nucleus and liver. USP2 variants influence energy metabolism by controlling hepatic gluconeogenesis, hepatic cholesterol uptake, adipose tissue inflammation, and subsequent systemic insulin sensitivity. USP2 also has the potential to promote surface expression of ion channels in renal and intestinal epithelial cells. In addition to modifying the production of cytokines in immune cells, USP2 also modulates the signaling molecules that are involved in cytokine signaling in the target cells. Usp2 knockout mice exhibit changes in locomotion and male fertility, which suggest roles for USP2 in the central nervous system and male genital tract, respectively. In this review, we summarize the cellular events with USP2 contributions and list the signaling molecules that are upstream or downstream of USP2. Additionally, we describe phenotypic differences found in the in vitro and in vivo experimental models.

show abstract