المؤلفون: dela Peña, Ike C., Figueroa, Johnny D., Shi, Wei‐Xing

المساهمون: National Institutes of Health, American Association of Colleges of Pharmacy

المصدر: Pharmacology Research & Perspectives ; volume 10, issue 3 ; ISSN 2052-1707 2052-1707

الوصف: The prolonged exposure to obesogenic diets disrupts the mesocortical dopaminergic input to the prefrontal cortex (PFC). This leads to suboptimal dopamine levels in this brain region, which affects cognition and control of food intake. Treatments that restore mesocortical dopaminergic neurotransmission may improve obesity‐associated cognitive dysfunction and modulate food intake to induce weight loss. Given the complexity and multifactorial nature of obesity, combination treatments would likely achieve sizeable and sustained body weight loss and improve obesity‐linked outcomes, such as cognitive dysfunction. Given this background, we hypothesize that concomitant activation of serotonin 5‐HT2C and histamine H1 receptors, coupled with antagonism of histamine H3 receptors, synergistically modulates mesocortical dopamine neurotransmission and ameliorates obesity‐induced cognitive dysfunction. We propose to test the hypothesis in a diet‐induced obesity (DIO) rat model by treating animals with the 5‐HT2C agonist lorcaserin and the H1 agonist and H3 antagonist betahistine. Consistent with our hypothesis, both lorcaserin and betahistine have been shown to reduce body weight in humans with obesity and animals. Both drugs have been demonstrated to improve cognitive functions by influencing dopaminergic signaling in the PFC. The proposed combination treatment addresses the paucity of studies on obesity treatments that improve cognitive function. This research may also help identify a potential targetable mechanism connecting obesity and neurocognitive outcomes.

الإتاحة: https://doi.org/10.1002/prp2.947Test

المؤلفون: Liu, Xiu-Xiu, Chen, Xing-Hui, Zheng, Zhi-Wei, Jiang, Qin, Li, Chen, Yang, Lin, Chen, Xiang, Mao, Xing-Feng, Yuan, Hao-Yang, Feng, Li-Li, Jiang, Quan, Shi, Wei-Xing, Sasaki, Takuya, Fukunaga, Kohji, Chen, Zhong, Han, Feng, Lu, Ying-Mei

المساهمون: National Natural Science Foundation of China

المصدر: Signal Transduction and Targeted Therapy ; volume 7, issue 1 ; ISSN 2059-3635

مصطلحات موضوعية: Cancer Research, Genetics

الوصف: Cerebellar ataxias are characterized by a progressive decline in motor coordination, but the specific output circuits and underlying pathological mechanism remain poorly understood. Through cell-type-specific manipulations, we discovered a novel GABAergic Purkinje cell (PC) circuit in the cerebellar IV/V lobe that projected to CaMKIIα + neurons in the fastigial nucleus (FN), which regulated sensorimotor coordination. Furthermore, transcriptomics profiling analysis revealed various cerebellar neuronal identities, and we validated that biorientation defective 1 (BOD1) played an important role in the circuit of IV/V lobe to FN. BOD1 deficit in PCs of IV/V lobe attenuated the excitability and spine density of PCs, accompany with ataxia behaviors. Instead, BOD1 enrichment in PCs of IV/V lobe reversed the hyperexcitability of CaMKIIα + neurons in the FN and ameliorated ataxia behaviors in L7-Cre ; BOD1 f/f mice. Together, these findings further suggest that specific regulation of the cerebellar IV/V lobe PCs → FN CaMKIIα+ circuit might provide neuromodulatory targets for the treatment of ataxia behaviors.

الإتاحة: https://doi.org/10.1038/s41392-022-00989-xTest
https://www.nature.com/articles/s41392-022-00989-x.pdfTest
https://www.nature.com/articles/s41392-022-00989-xTest

المؤلفون: Wang, Fei, Shi, Wei-Xing, Chen, Jie, He, Kang, Fang, Wei

المساهمون: Scientific Research Project of Health and Family Planning Commission of Hubei Province

المصدر: Medicine ; volume 100, issue 47, page e27583 ; ISSN 0025-7974 1536-5964

الوصف: Background: Osteoarthritis (OA) has been identified as a common musculoskeletal condition. As a chronic condition, OA adversely impact the hip and knee joints. Surgical treatment for hip and knee osteoarthritis is associated with high financial and long recovery processes. Therefore, patients are continually searching for alternative methods of treatment. Diacerein is regarded as symptom-modifying, slow-acting drug that could most likely change the disease structure of OA. The present systematic review protocol explains methods utilized to evaluate the clinical therapeutic effects of combining diacerein and glucosamine to treat OA. Methods: The authors will conduct a search for randomized controlled trials comparing diacerein plus glucosamine with diacerein alone, glucosamine alone, or another treatment in patients with OA. The search will be done in the following online-based databases: EMBASE, MEDLINE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and WanFang Database. All related RCTs included from inception to September 29, 2021 are included. Two authors will independently conduct data abstraction and quality assessment, and the comparative analysis will compare the results. The present meta-analysis will be performed with the RevMan software (version 5.3), where the results will be expressed as relative risk, mean differences, or standardized mean differences with 95% confidence intervals. Results: This study will be conducted to evaluate the clinical therapeutic effects of combined diacerein and glucosamine in the treatment of OA. Conclusion: The summary presented in the study will ascertain whether diacerein plus glucosamine intervention is an efficient and feasible method of treatment for OA patients. Trial registration number: 10.17605/OSF.IO/VHPZC

الإتاحة: https://doi.org/10.1097/md.0000000000027583Test

المؤلفون: Shen, Guofang, Shi, Wei-Xing

المصدر: Frontiers in Pharmacology ; volume 12 ; ISSN 1663-9812

مصطلحات موضوعية: Pharmacology (medical), Pharmacology

الوصف: Cortical neurons oscillate between Up and Down states during slow wave sleep and general anesthesia. Recent studies show that Up/Down oscillations also occur during quiet wakefulness. Arousal eliminates Down states and transforms Up/Down oscillations to a persistent Up state. Further evidence suggests that Up/Down oscillations are crucial to memory consolidation, whereas their transition to a persistent Up state is essential for arousal and attention. We have shown that D -amphetamine promotes cortical Up state, and the effect depends on activation of central α 1A adrenergic receptors. Here, we report that dopamine also plays a role in D -amphetamine’s effect. Thus, using local-field-potential recording in the prefrontal cortex in chloral hydrate-anesthetized rats, we showed that the Up-state promoting effect of D -amphetamine was attenuated by antagonists at either D1 or D2-like dopamine receptors. The effect was also partially mimicked by co-activation of D1 and D2-like receptors. These results are consistent with the fact that D -amphetamine increases the release of both norepinephrine and dopamine. They are also in agreement with studies showing that dopamine promotes wakefulness and mediates D -amphetamine-induced emergence from general anesthesia. The effect of D -amphetamine was not mimicked, however, by activation of either D1 or D2-like receptors alone, indicating an interdependence between D1 and D2-like receptors. The dopamine/norepinephrine precursor L-DOPA also failed to promote the Up state. While more studies are needed to understand the difference between L-DOPA and D -amphetamine, our finding may provide an explanation for why L-DOPA lacks significant psychostimulant properties and is ineffective in treating attention-deficit/hyperactivity disorder.

الإتاحة: https://doi.org/10.3389/fphar.2021.728729Test

المؤلفون: Sklair-Tavron, Liora, Shi, Wei-Xing, Lane, Sarah B., Harris, Herbert W., Bunney, Benjamin S., Nestler, Eric J.

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 1996 Oct 01. 93(20), 11202-11207.

الوصول الحر: https://www.jstor.org/stable/40307Test

المؤلفون: Shao, Ling-Xiao, Jiang, Quan, Liu, Xiu-Xiu, Gong, Dong-Mei, Yin, Yi-Xuan, Wu, Gang, Sun, Ning-He, Wang, Cheng-Kun, Chen, Qiao-Zhen, Yu, Chao, Shi, Wei-Xing, Fan, Heng-Yu, Fukunaga, Kohji, Chen, Zhong, Lu, Ying-Mei, Han, Feng

المصدر: Molecular Psychiatry ; volume 24, issue 10, page 1399-1399 ; ISSN 1359-4184 1476-5578

مصطلحات موضوعية: Cellular and Molecular Neuroscience, Psychiatry and Mental health, Molecular Biology

الإتاحة: https://doi.org/10.1038/s41380-019-0523-0Test
https://www.nature.com/articles/s41380-019-0523-0.pdfTest
https://www.nature.com/articles/s41380-019-0523-0Test

المؤلفون: Liu, Xiu-xiu, Yang, Lin, Shao, Ling-xiao, He, Yang, Wu, Gang, Bao, Yu-huan, Lu, Nan-nan, Gong, Dong-mei, Lu, Ya-ping, Cui, Tian-tian, Sun, Ning-he, Chen, Dan-yang, Shi, Wei-xing, Fukunaga, Kohji, Chen, Hong-shan, Chen, Zhong, Han, Feng, Lu, Ying-mei

المساهمون: National Key Research and Development Program of China, National Natural Science Foundation of China, Nanjing Medical University

المصدر: Journal of Experimental Medicine ; volume 217, issue 1 ; ISSN 0022-1007 1540-9538

الوصف: Blood–brain barrier (BBB) dysfunction has been suggested to play an important role in epilepsy. However, the mechanism mediating the transition from cerebrovascular damage to epilepsy remains unknown. Here, we report that endothelial cyclin-dependent kinase 5 (CDK5) is a central regulator of neuronal excitability. Endothelial-specific Cdk5 knockout led to spontaneous seizures in mice. Knockout mice showed increased endothelial chemokine (C-X-C motif) ligand 1 (Cxcl1) expression, decreased astrocytic glutamate reuptake through the glutamate transporter 1 (GLT1), and increased glutamate synaptic function. Ceftriaxone restored astrocytic GLT1 function and inhibited seizures in endothelial Cdk5-deficient mice, and these effects were also reversed after silencing Cxcl1 in endothelial cells and its receptor chemokine (C-X-C motif) receptor 2 (Cxcr2) in astrocytes, respectively, in the CA1 by AAV transfection. These results reveal a previously unknown link between cerebrovascular factors and epileptogenesis and provide a rationale for targeting endothelial signaling as a potential treatment for epilepsy.

الإتاحة: https://doi.org/10.1084/jem.20180992Test

المؤلفون: Chen, Dan-Yang, Sun, Ning-He, Lu, Ya-Ping, Hong, Ling-Juan, Cui, Tian-Tian, Wang, Cheng-Kun, Chen, Xing-Hui, Wang, Shuai-Shuai, Feng, Li-Li, Shi, Wei-Xing, Fukunaga, Kohji, Chen, Zhong, Lu, Ying-Mei, Han, Feng

المصدر: Theranostics ; volume 9, issue 20, page 5937-5955 ; ISSN 1838-7640

مصطلحات موضوعية: Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Medicine (miscellaneous)

الإتاحة: https://doi.org/10.7150/thno.34168Test
http://www.thno.org/v09p5937.htmTest

المؤلفون: Tan, Chao, Lu, Nan-Nan, Wang, Cheng-Kun, Chen, Dan-Yang, Sun, Ning-He, Lyu, Hang, Körbelin, Jakob, Shi, Wei-Xing, Fukunaga, Kohji, Lu, Ying-Mei, Han, Feng

المساهمون: NIH/NIBIB, State Key Program of National Natural Science of China, National Key Research and Development Program of China, National Natural Science Foundations of China

المصدر: Neuron ; volume 101, issue 5, page 920-937.e13 ; ISSN 0896-6273

الإتاحة: https://doi.org/10.1016/j.neuron.2018.12.036Test
https://api.elsevier.com/content/article/PII:S0896627318311565?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0896627318311565?httpAccept=text/plainTest

المؤلفون: Liu, Chang-Liang, Wang, Ya-Kun, Jin, Guo-Zhang, Shi, Wei-Xing, Gao, Ming

المصدر: Scientific Reports ; volume 8, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: The initiation of psychostimulant sensitization depends on the mesocorticolimbic dopamine (DA) system. Although many cellular adaptations has been reported to be associated with this addictive behavior, the overall influence of these adaptations on the network regulation of DA neurons has not been established. Here, we profile a network-driven slow oscillation (SO) in the firing activity of ventral tegmental area (VTA) putative DA and non-DA neurons and their correlation with locomotor sensitization induced by repeated administration of cocaine. One day after the last cocaine injection, the power of SO (Pso) significantly increased both in DA and non-DA neurons. Interestingly, the Pso in DA neurons was positively correlated, while Pso in non-DA neurons was negatively correlated with the level of locomotor sensitization. On the other hand, the firing rates of DA and non-DA neurons were both elevated, but none exhibited any correlation with the level of sensitization. Fourteen days after the last injection, the Pso of DA neurons dissipated but still positively correlated with the level of sensitization. In contrast, the Pso in non-DA neurons lost correlation with locomotor sensitization. These results suggest that cocaine-induced locomotor sensitization is associated with long-term network adaptation in DA system and that DA and non-DA neurons may corporately facilitate/hamper the initiation of locomotor sensitization.

الإتاحة: https://doi.org/10.1038/s41598-018-21592-7Test
https://www.nature.com/articles/s41598-018-21592-7Test
https://www.nature.com/articles/s41598-018-21592-7.pdfTest