Cognitive impairment in Alzheimer's disease FAD4T mouse model: Synaptic loss facilitated by activated microglia via C1qA.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized by cognitive dysfunction. The connection between neuroinflammation and abnormal synaptic function in AD is recognized, but the underlying mechanisms remain unclear. In this study, we utilized a mouse model of AD, FAD4T mice aged 6-7 months, to investigate the molecular changes affecting cognitive impairment. Behavior tests showed that FAD4T mice exhibited impaired spatial memory compared with their wild-type littermates. Immunofluorescence staining revealed the presence of Aß plaques and abnormal glial cell activation as well as changes in microglial morphology in the cortex and hippocampus of FAD4T mice. Synaptic function was impaired in FAD4T mice. Patch clamp recordings of hippocampal neurons revealed reduced amplitude of miniature excitatory postsynaptic currents. Additionally, Golgi staining showed decreased dendritic spine density in the cortex and hippocampus of FAD4T mice, indicating aberrant synapse morphology. Moreover, hippocampal PSD-95 and NMDAR1 protein levels decreased in FAD4T mice. RNA-seq analysis revealed elevated expression of immune system and proinflammatory genes, including increased C1qA protein and mRNA levels, as well as higher expression of TNF-α and IL-18. Taken together, our findings suggest that excessive microglia activation mediated by complement factor C1qA may contribute to aberrant synaptic pruning, resulting in synapse loss and disrupted synaptic transmission, ultimately leading to AD pathogenesis and behavioral impairments in the FAD4T mouse model. Our study provides valuable insights into the underlying mechanisms of cognitive impairments and preliminarily explores a potentially effective treatment approach targeting on C1qA for AD.

A dendrite-free and anticaustic Zn anode enabled by high current-induced reconstruction of the electrical double layer.

Aqueous Zn-based batteries deliver thousands of cycles at high rates but poor recyclability at low rates. Herein, we reveal that this illogical phenomenon is attributed to the reconstructed electrode/electrolyte interface at high rates, wherein the condensed electrical double layer (EDL) and the tightly absorbed Zn2+ ions on the Zn electrode surface afford compact and corrosion-resistant Zn deposits.

High-Energy and Long-Lived Zn-MnO2 Battery Enabled by a Hydrophobic-Ion-Conducting Membrane.

Alkaline Zn-MnO2 batteries feature high security, low cost, and environmental friendliness while suffering from severe electrochemical irreversibility for both the Zn anode and MnO2 cathode. Although neutral electrolytes are supposed to improve the reversibility of the Zn anode, the MnO2 cathode indeed experiences a capacity degradation caused by the Jahn-Teller effect of the Mn3+ ion, thus shortening the lifespan of the neutral Zn-MnO2 batteries. Theoretically, the MnO2 cathode undergoes a highly reversible two-electron redox reaction of the MnO2/Mn2+ couple in strongly acidic electrolytes. However, acidic electrolytes would inevitably accelerate the corrosion of the Zn anode, making long-lived acidic Zn-MnO2 batteries impossible. Herein, to overcome the challenges faced by Zn-MnO2 batteries, we propose a hybrid Zn-MnO2 battery (HZMB) by coupling the neutral Zn anode with the acidic MnO2 cathode, wherein the neutral anode and acidic cathode are separated by a proton-shuttle-shielding and hydrophobic-ion-conducting membrane. Benefiting from the optimized reaction conditions for both the MnO2 cathode and Zn anode as well as the well-designed membrane, the HZMB exhibits a high working voltage of 2.05 V and a long lifespan of 2275 h (2000 cycles), breaking through the limitations of Zn-MnO2 batteries in terms of voltage and cycle life.

Decoupled aqueous batteries using pH-decoupling electrolytes.

Aqueous batteries have been considered as the most promising alternatives to the dominant lithium-based battery technologies because of their low cost, abundant resources and high safety. The output voltage of aqueous batteries is limited by the narrow stable voltage window of 1.23 V for water, which theoretically impedes further improvement of their energy density. However, the pH-decoupling electrolyte with an acidic catholyte and an alkaline anolyte has been verified to broaden the operating voltage window of the aqueous electrolyte to over 3 V, which goes beyond the voltage limitations of the aqueous batteries, making high-energy aqueous batteries possible. In this Review, we summarize the latest decoupled aqueous batteries based on pH-decoupling electrolytes from the perspective of ion-selective membranes, competitive redox couples and potential battery prototypes. The inherent defects and problems of these decoupled aqueous batteries are systematically analysed, and the critical scientific issues of this battery technology for future applications are discussed.