Background: Heat stroke is the outcome of excessive heat stress, which results in core temperatures exceeding 40°C accompanied by a series of complications. The brain is particularly vulnerable to damage from heat stress. In our previous studies, both activated microglia and increased neuronal autophagy were found in the cortices of mice with heat stroke. However, whether activated microglia can accelerate neuronal autophagy under heat stress conditions is still unknown. In this study, we aimed to investigate the underlying mechanism that caused neuronal autophagy upregulation in heat stroke from the perspective of exosome-mediated intercellular communication.
Methods: In this study, BV2 and N2a cells were used instead of microglia and neurons, respectively. Exosomes were extracted from BV2 culture supernatants by ultracentrifugation and then characterized transmission electron microscopy, nanoparticle tracking analysis and Western blotting. N2a cells pretreated with/without miR-155 inhibitor were cocultured with microglial exosomes that were treated with/without heat stress or miR-155 overexpression and subsequently subjected to heat stress treatment. Autophagy in N2a cells was assessed by detecting autophagosomes and autophagy-related proteins through transmission electron microscopy, immunofluorescence, and Western blotting. The expression of miR-155 in BV2 and BV2 exosomes and N2a cells was measured using real-time reverse transcription polymerase chain reaction. Target binding analysis was verified a dual-luciferase reporter assay.
Results: N2a autophagy moderately increased in response to heat stress and accelerated by BV2 cells through transferring exosomes to neurons. Furthermore, we found that neuronal autophagy was positively correlated with the content of miR-155 in microglial exosomes. Inhibition of miR-155 partly abolished autophagy in N2a cells, which was increased by coculture with miR-155-upregulated exosomes. Mechanistic analysis confirmed that Rheb is a functional target of miR-155 and that microglial exosomal miR-155 accelerated heat stress-induced neuronal autophagy mainly by regulating the Rheb-mTOR signaling pathway.
Conclusion: Increased miR-155 in microglial exosomes after heat stroke can induce neuronal autophagy their transfer into neurons. miR-155 exerted these effects by targeting Rheb, thus inhibiting the activity of mTOR signaling. Therefore, miR-155 could be a promising target for interventions of neuronal autophagy after heat stroke.
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http://dx.doi.org/10.3389/fncel.2022.865568 | DOI Listing |
Cell Mol Biol (Noisy-le-grand)
November 2024
Eskişehir Osmangazi University, Medical Faculty, Department of Biostatistics, Eskişehir, Türkiye.
Neuroblastoma shows the highest lethality in childhood and has poor prognosis at high grade. Our objectives included determining how retinoic acid affected the growth of neuroblastoma cells and the relationship between chemicals unique to neurons and cell death processes like apoptosis and mitophagy. The 50% inhibitory concentration of retinoic acid on SH-SY5Y neuroblastoma cells was determined at the 24th, 48th and 72nd hours.
View Article and Find Full Text PDFJ Neuropathol Exp Neurol
December 2024
Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Ischemic strokes pose serious risks to human health. We aimed to elucidate the function of NOD-like receptor X1 (NLRX1) in a rat middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injury (CIRI) model and in an oxygen-glucose deprivation/reperfusion (OGD/R)-treated human microglial cell line (HMC3) model. Following NLRX1 upregulation, infarct volumes were measured with 2,3,5-triphenyltetrazolium chloride staining and pathological examination was conducted with hematoxylin-eosin staining.
View Article and Find Full Text PDFCell Biol Toxicol
December 2024
Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China.
Existing evidence indicates that exercise training can enhance neural function by regulating mitochondrial quality control (MQC), which can be impaired by cerebral ischemia, and that sirtuin-3 (SIRT3), a protein localized in mitochondria, is crucial in maintaining mitochondrial functions. However, the relationship among exercise training, SIRT3, and MQC after cerebral ischemia remains obscure. This study attempted to elucidate the relationship among exercise training, SIRT3 and MQC after cerebral ischemia in rats.
View Article and Find Full Text PDFEur J Med Chem
December 2024
Department of Pharmacy, University of Pisa, via Bonanno 6, 56126, Pisa, Italy; Centre for Instrumentation Sharing, University of Pisa (CISUP), Italy. Electronic address:
Alzheimer's disease (AD) represents one of the main challenges for the 21st century medical research as no disease-modifying agent has been successfully progressed to the market, while the number of people affected by AD is estimated to grow exponentially over the next years. The complex network of triggering factors involved in the insurgence and progression of AD can be rightly addressed as one of the main reasons behind the difficulty in identifying new pharmacological approaches. For this reason, the discovery and development of drugs endowed with pleiotropic activity remain the most valuable, but at the same time challenging, approaches to tackle down AD.
View Article and Find Full Text PDFMol Brain
December 2024
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jian-She Road, Zhengzhou, 450052, Henan, China.
Objective: Cerebral ischemia-reperfusion injury (CIRI) is a major obstacle to neurological recovery after clinical treatment of ischemic stroke. The aim of this study was to investigate the molecular mechanism of Nek6 alleviating CIRI through autophagy after cerebral ischemia.
Materials And Methods: A mouse model of CIRI was constructed by middle cerebral artery occlusion (MCAO).
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