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Abstract The core of clinic treatment of Parkinson's disease (PD) is to enhance dopamine (DA) signaling within the brain. The regulation of dopamine transporter (DAT) is integral to this process. This study aims to explore the regulatory mechanism of glial cell line-derived neurotrophic factor (GDNF) on DAT, thereby gaining a profound understanding its potential value in treating PD. In this study, we investigated the effects of GDNF on both cellular and mouse models of PD, including the glycosylation and membrane transport of DAT detected by immunofluorescence and immunoblotting, DA signal measured by neurotransmitter fiber imaging technology, Golgi morphology observed by electron microscopic, as well as cognitive ability assessed by behavior tests. This study revealed that in animal trials, MPTP-induced Parkinson's Disease (PD) mice exhibited a marked decline in cognitive function. Utilizing ELISA and neurotransmitter fiber imaging techniques, we observed a decrease in dopamine levels and a significant reduction in the intensity of dopamine signal release in the Prefrontal Cortex (PFC) of PD mice induced by MPTP. Intriguingly, these alterations were reversed by Glial Cell Line-Derived Neurotrophic Factor (GDNF). In cellular experiments, following MPP + intervention, there was a decrease in Gly-DAT modification in both the cell membrane and cytoplasm, coupled with an increase in Nongly-DAT expression and aggregation of DAT within the cytoplasm. Conversely, GDNF augmented DAT glycosylation and facilitated its membrane transport in damaged dopaminergic neurons, concurrently reversing the effects of GRASP65 depletion and Golgi fragmentation, thereby reducing the accumulation of DAT in the Golgi apparatus. Furthermore, overexpression of GRASP65 enhanced DAT transport in PD cells and mice, while suppression of GRASP65 attenuated the efficacy of GDNF on DAT. Additionally, GDNF potentiated the reutilization of neurotransmitters by the PFC presynaptic membrane, boosting the effective release of dopamine following a single electrical stimulation, ultimately ameliorating the cognitive impairments in PD mice.Therefore, we propose that GDNF enhances the glycosylation and membrane trafficking of DAT by facilitating the re-aggregation of the Golgi apparatus, thereby amplifying the utilization of DA signals. This ultimately leads to the improvement of cognitive abilities in PD mouse models. Our study illuminates, from a novel angle, the beneficial role of GDNF in augmenting DA utilization and cognitive function in PD, providing fresh insights into its therapeutic potential.

This study focused on α -synuclein (α -syn) aggregation in the dorsomedial striatum (DMS) so as to investigate its role in the cognitive flexibility of Parkinson's disease (PD). Here, we investigated the cognitive flexibility by assessing reversal learning abilities in MPTP-induced subacute PD model mice and in C57BL/6J mice with α -syn aggregation in the DMS induced by adenovirus (AAV-SNCA) injection, followed by an analysis of the target protein's expression and distribution. PD mice exhibited impairments in reversal learning, positively correlated with the expression of phosphorylated α -syn in the DMS. Furthermore, the mice in the AAV-SNCA group exhibited reversal learning deficits and a reduction in acetylcholine levels, accompanied by protein alterations within the DMS. Notably, the administration of a muscarinic receptor 1 (M1R) agonist was able to alleviate the aforementioned phenomenon. These findings suggest that the impaired cognitive flexibility in PD may be attributed to the diminished activation of acetylcholine to M1R caused by α -syn aggregation. [ABSTRACT FROM AUTHOR]

Aqueous zinc‐ion batteries (ZIBs) hold significant promise for large‐scale energy storage. While considerable strides have been made in modifying separators, the challenge of developing dendrite‐free, corrosion‐resistant, and cost‐effective separators for achieving extended cycling performance of Zn anodes persists. In light of this, a TiO2 coating separator to mitigate interfacial corrosion and passivation reactions, thereby facilitating high‐performance ZIBs is designed. This study delves into the influence of the loading amount and crystal phase of the TiO2 coating layers on separator modification. Zn symmetric cells employing the anatase TiO2‐modified glass fiber (A‐TiO2@GF) separator demonstrate superior Zn2+ ion transport kinetics in a mild ZnSO4 electrolyte, ensuring sustained long‐term stability and uniform Zn deposition. Furthermore, the reduced hydrogen evolution reaction (HER) activity of A‐TiO2 coatings curbs H+ ion migration, minimizing interfacial corrosion and HER. Consequently, the assembled Zn||CaV8O20 zinc‐ion full cells demonstrate outstanding long‐term durability and impressive specific capacity, boasting a discharge capacity of 142 mAh g−1 after 1000 cycles. This work introduces a straightforward interface engineering strategy for creating efficient separators in zinc‐ion batteries, promoting uniform Zn deposition. [ABSTRACT FROM AUTHOR]

Aqueous zinc ion batteries (AZIBs) have stimulated extensive attention due to their environmental friendliness and low cost. Unfortunately, the inevitable dendrite growth and corrosion on the zinc (Zn) anode severely hinder the practical application of AZIBs. Herein, an amino acid containing an imidazole group is introduced as an effective additive to address these issues. The dynamic conversion of amino acid and protonated amino acid creates a pH buffer function that regulates solution pH in real time, inhibits hydrogen evolution reaction (HER), and eliminates notorious by‐products. In addition, the protonated amino acid is preferentially adsorbed on the Zn anode, preventing contact of the active water with the Zn surface and promoting homogeneous Zn deposition. Thus, the amino acid‐based electrolyte promotes dendrite free plating/stripping with a Coulombic efficiency up to 99.67% and cycle lifetime of 2600 h. In particular, a depth of discharge of up to 87% can be achieved with an ultra‐high areal capacity of 24 mAh cm−2. The developed Zn||CVO full cell also exhibits better electrochemical performance than that without additives. This work provides an effective and convenient approach for safe and efficient Zn‐ion batteries. [ABSTRACT FROM AUTHOR]

ABSTRACT Titanium dioxide nanoparticles (TiO2 NPs) have been used in environmental management, food, medicine, and industry. But TiO2 NPs have been demonstrated to cross the blood-brain barrier and store up in the brain organization, leading to glutamate-mediated neurotoxicity. However, the neurotoxicity in the brain is not well understood. In this study, mice were exposed to 1.25, 2.5, or 5 mg/kg body weight TiO2 NPs for 9 months, and the glutamate-glutamine cyclic pathway and expressions of glutamate receptors associated with the hippocampal neurotoxicity were investigated. Our findings showed elevations of glutamate release and phosphate-activated glutaminase activity, and reductions in glutamine and glutamine synthetase in the hippocampus following exposure to TiO2 NPs. Furthermore, TiO2 NPs significantly inhibited the expression of N-methyl- d-aspartate receptor subunits (including NR1, NR2A, and NR2B) and metabotropic glutamate receptor 2 in mouse hippocampus. These findings suggest that the imbalance of glutamate metabolism triggered inhibitions of glutamate receptor expression in the TiO2 NP-exposed hippocampus. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 655-662, 2016. [ABSTRACT FROM AUTHOR]