Apoptosis signal-regulating kinase 1 (ASK1) may play a pivotal role in reactive gliosis. To assess the role of ASK1 in trauma-induced reactive gliosis, we examined the phosphorylation of ASK1 and the expression of glial fibrillary acidic protein (GFAP) and vimentin after scratch injury in cultured astrocytes and spinal cord injury (SCI) in rats. Enhanced phosphorylation of ASK1 was detected during reactive gliosis both in vitro and in vivo, and P38 MAPK relayed the signal from phosphorylated ASK1 to the activation of astrocytes. Immunoprecipitation analyses suggested that 14-3-3 was dissociated from ASK1 during astrocyte activation. Finally, treatment with thioredoxin reduced ASK1 phosphorylation and reactive gliosis and promoted hindlimb locomotion recovery in SCI rats. These results indicated that ASK1 may play an important role in mechanical-injury-induced reactive gliosis.
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http://dx.doi.org/10.1016/j.neulet.2019.134675 | DOI Listing |
Biomolecules
December 2024
Department of Anatomy and Developmental Biology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Shimane, Japan.
The prognosis of spinal cord injury (SCI) is closely linked to secondary injury processes, predominantly driven by neuroinflammation. Interleukin-18 (IL-18) plays a pivotal role in this inflammatory response. In previous work, we developed an anti-IL-18 antibody capable of neutralizing the active form of IL-18.
View Article and Find Full Text PDFNeurobiol Dis
January 2025
Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada. Electronic address:
The consequences of non-pathogenic huntingtin (HTT) reduction in the mature brain are of substantial importance as clinical trials for numerous HTT-lowering therapies are underway; many of which are non-selective in that they reduce both mutant and wild type protein variants. In this study, we injected CaMKII-promoted AAV-Cre directly into the hippocampus of adult HTT floxed mice to explore the role of wild-type huntingtin (wtHTT) in adult hippocampal pyramidal neurons and the broader implications of its loss. Our findings reveal that wtHTT depletion results in profound macroscopic morphological abnormalities in hippocampal structure, accompanied by significant reactive gliosis.
View Article and Find Full Text PDFCells
January 2025
Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences & Technology, Gachon University, Incheon 21999, Republic of Korea.
Stroke affects over 12 million people annually, leading to high mortality, long-term disability, and substantial healthcare costs. Although East Asian herbal medicines are widely used for stroke treatment, the pathways of operation they use remain poorly understood. Our study investigates the neuroprotective properties of (AM) in acute ischemic stroke using photothrombotic (PTB) and transient middle cerebral artery occlusion (tMCAO) mouse models, as well as an oxygen-glucose deprivation (OGD) model.
View Article and Find Full Text PDFMethods Protoc
January 2025
The Krieger Eye Research Laboratory, Bruce and Ruth Faculty of Medicine, Technion-Institute of Technology, Haifa 3525433, Israel.
Cobalt is a trace element, crucial for red blood cell formation and neurological function. Cobalt toxicity is often only diagnosed after severe manifestations, including visual impairment. We aimed to investigate whether optical coherence tomography (OCT) and magnetic resonance imaging (MRI) can effectively detect cobalt-induced ocular toxicity in a murine model.
View Article and Find Full Text PDFBr J Pharmacol
January 2025
Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.
Background And Purpose: Inflammatory bowel disease (IBD) patients display genetic polymorphisms in toll-like receptor 4 (TLR4) genes, contributing to dysregulate enteric nervous system (ENS) circuits with increased levels of 5-HT and alteration of the neuroimmune crosstalk. In this study, we investigated the impact of TLR4 signalling on mouse ENS dysfunction caused by dextran sulphate sodium (DSS)-induced ileitis.
Experimental Approach: Male C57BL/6J (wild-type [WT]) and TLR4 mice (10 ± 2 weeks old) received 2% DSS in drinking water for 5 days and then were switched to 3-day regular drinking water.
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