The Latest Articles on Neuropharmacology

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles on Neuropharmacology.

Title: MicroRNA-124-3p alleviates cerebral ischaemia-induced neuroaxonal damage by enhancing Nrep expression
Authors: Peng Huang, Songren Wei, Jing Ren, Zhuohong Tang, Mingjuan Guo, Fen Situ, Dan Zhang, Jianghua Zhu, Li Xiao, Jiangping Xu, Guoqing Liu
Type: Research Article
Abstract:
Objective: Ischaemic stroke has a high death rate and frequently results in long-term and severe brain damage in survivors. miRNA-124-3p (miR-124-3p) treatment has been suggested to reduce ischaemia and play a vital function in avoiding neuron death. An investigation of the role of miR-124-3p, in the ischaemia damage repair or protection in the middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation/reperfusion (OGD/R) model, was the purpose of this research. Methods: The expression of miRNA and mRNA in the MCAO model was predicted using bioinformatics analysis. The OGD/R neuronal model was developed. We examined the influence of a number of compounds on the OGD/R model in vitro using gain- and loss-of-function approaches. Results: For starters, miR-124-3p and Nrep level in the MCAO model were found to be lower in the model predicted by bioinformatics than in the sham-operated group. And then in the OGD/R model, miR-124-3p treatment reduced OGD/R neuronal damage, increased neuronal survival, and reduced apoptosis in cell lines. Moreover, we further looked at the impact of miR-124-3p on downstream Rnf38 and Nrep using the OGD/R model. Western blot analysis and dual-luciferase reporter assays indicated that miR-124-3p binds and inhibits Rnf38. Finally, although Nrep expression was reduced in the OGD/R model neuronal model, it was shown that miR-124-3p administration reduced apoptosis and increased neuronal activity, particularly with regard to axon regeneration-related proteins. Conclusion: Our studies have shown that miR-124-3p may reduce neuronal injury by preventing Rnf38-mediated effects on the Nrep axis.
Access this article: https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106949

Title: Protective effect of kaempferol against cognitive and neurological disturbances induced by d-galactose and aluminum chloride in mice
Authors: He Lin, Xinhe Wang, Jiarui Zhao, Zhe Lin
Type: Research Article
Abstract:
In this work, d-galactose/aluminum chloride (AlCl3)-treated mice with cognitive and neurological disturbances were administered kaempferol for 30 days. The results showed that kaempferol significantly improved learning and memory in step down test and morris water maze test, decreased the contents of brain ROS, MDA, IL-1β, IL-6 and TNF-α, increased the activity of SOD and GSH-Px, and regulated the SIRT1/NF-κB signal pathway in the brain. Also kaempferol increased the contents of γ-aminobutyric acid, glycine, acetylcholine and dopamine, and decreased the contents of glutamate,a spartic acid and glutamate to γ-aminobutyric acid ratio obviously. A total of 12 potential biomarkers were clearly altered after kaempferol treatment in the metabolomics, which related to phenylalanine, tyrosine and tryptophan biosynthesis, primary bile acid biosynthesis, amino acid metabolism and glycerophospholipid metabolism. To conclude, our study verified the neuroprotective effect of kaempferol on d-galactose/AlCl3-treated mice and serve as a potential nutraceutical agent for cognitive and neurological dysfunction.
Access this article: https://doi.org/10.1016/j.jff.2022.105385

Title: Biomimetic hybrid scaffold containing niosomal deferoxamine promotes angiogenesis in full-thickness wounds
Authors: Shirin Nour, Rana Imani, Mehrnaz Mehrabani, Atefeh Solouk, Maryam Iranpour, Sasan Jalili-Firoozinezhad, Ali Mohammad Sharifi
Type: Research Article
Abstract:
Effective management of full-thickness wounds faces significant challenges due to poor angiogenesis and impaired healing. Biomimetic tissue-engineered scaffolds with angiogenic properties can, however, enhance the regeneration capacity of the damaged skin. Here, we developed a hybrid double-layer nanofibrous scaffold, comprised of egg white (EW) and polyvinyl alcohol (PVA), loaded with niosomal Deferoxamine (NDFO) for enhanced angiogenesis and wound healing features. The hybrid scaffold showed enhanced mechanical properties with comparable modulus and shape-recovery behavior of the human skin. Thanks to the porous morphology and uniform distribution of NDFO within the nanofibers, in vitro drug release studies indicated controlled and sustained release of DFO for up to 9 days. The constructs also promoted a significant increase in vascular sprouting area in vitro and enhanced vascular branches ex vivo. In vivo, implantation of the hybrid scaffold in full-thickness wounds in rats revealed early angiogenic response, a higher number of neo-formed vessels, a faster healing rate and complete epithelialization as early as day 10, compared to the control groups. Thus, the presented biomimetic hybrid scaffold with DFO control release features holds great promise in accelerated full-thickness wound healing and soft tissue regeneration.
Access this article: https://doi.org/10.1016/j.mtchem.2022.101314

Title: GluN2D expression is regulated by restraint stress and supports active stress coping bouts
Authors: Marie A. Doyle, Jordan A. Brown, Danny G. Winder
Type: Research Article
Abstract:
Stress coping strategies represent critical responses to environmental challenges, and active coping has been linked to stress resilience in humans. Understanding the neuroadaptations that support these strategies may provide insights into adaptive and maladaptive stress responses. NMDA receptors (NMDARs) play key roles in neuroadaptation, and NMDARs have been specifically implicated in stress responsiveness. Constitutive knockout mice have been used to implicate the GluN2D NMDAR subunit in regulation of stress-sensitive and affective behavior, but the brain regions in which GluN2D expression changes drive these effects remain unknown. Here we report that following an acute restraint stressor, GluN2D subunit expression is specifically decreased in the bed nucleus of the stria terminalis (BNST), a key region involved in stress processing, in male but not female mice, with no differences found in the thalamus or ventral hippocampus in either sex. Rodents engage in active struggling events during restraint stress that may represent active coping strategies to stress. Thus, we assessed active coping bouts during acute and chronic restraint stress sessions in GluN2D knockout mice. During the first restraint session, GluN2D knockout mice exhibited a pronounced decrease in struggling bouts during restraint stress relative to wild-type littermates, consistent with a role of GluN2D in active coping responses to stress. Repeated, daily restraint sessions revealed a sex-specific role of GluN2D expression on certain aspects of active coping behaviors, with male GluN2D KO mice exhibiting a decrease in total coping bouts measured across five sessions. However, BNST-specific knockdown of GluN2D in male mice did not alter active coping bouts, suggesting either a multi-synaptic role of GluN2D and/or a developmental role of GluN2D in this behavior. Altogether, these data are consistent with a growing literature suggesting that exploration of GluN2D control of stress circuit actions may lead to a novel therapeutic target to consider for stress-related mood disorders.
Access this article: https://doi.org/10.1016/j.neuropharm.2022.109377

Title: Update on Therapeutic potential of emerging nanoformulations of phytocompounds in Alzheimer's and Parkinson's disease
Authors: Neha Kanojia, Komal Thapa, Gagandeep Kaur, Ameya Sharma, Vivek Puri, Nitin Verma
Type: Review
Abstract:
The prevalence of neurodegenerative disorders (NDs) has increased recently, with Parkinson's disease (PD) and Alzheimer's disease (AD) being the two utmost prevalent ones. As a result of the various defensive barriers that enclose the central nervous system (CNS), drug administration to the brain continues to be the most difficult aspect of treating all neurodegenerative illnesses. One of the novel methods for treating a wide range of disorders, including different types of cancer, neuronal issues, and infectious diseases, is nanotechnology. Currently, nanotechnology-based medicine has emerged as an effective treatment method for NDs. Therapeutics for AD and PD, which can target and administer medications across the blood-brain barrier (BBB), have created an interesting novel field for nanoformulation-based therapies. The exciting interface existing between medicinal plants and nanotechnology is an emerging marvel in medicine that has delivered promising results in the treatment of AD and PD. The present review aims to reveal the therapeutic potential of emerging nanoformulations of Phytocompounds for the treatment and management of AD and PD.
Access this article: https://doi.org/10.1016/j.jddst.2022.104074