Brain Structure & Function
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2024
·Vol. 229
·期 7
·1617-1629
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IF 2.7
Omholt Stig W.,Lejneva Raissa,Donate Maria Jose Lagartos,Caponio Domenica,Fang Evandro Fei,Kobro-Flatmoen Asgeir
In layer II of the entorhinal cortex, the principal neurons that project to the dentate gyrus and the CA3/2 hippocampal fields markedly express the large glycoprotein reelin (Re + ECLII neurons). In rodents, neurons located at the dorsal extreme of the EC, which border the rhinal fissure, express the highest levels, and the expression gradually decreases at levels successively further away from the rhinal fissure. Here, we test two predictions deducible from the hypothesis that reelin expression is strongly correlated with neuronal metabolic rate. Since the mitochondrial turnover rate serves as a proxy for energy expenditure, the mitophagy rate arguably also qualifies as such. Because messenger RNA of the canonical promitophagic BCL2 and adenovirus E1B 19-kDa-interacting protein 3 (Bnip3) is known to be highly expressed in the EC, we predicted that Bnip3 would be upregulated in Re + ECLII neurons, and that the degree of upregulation would strongly correlate with the expression level of reelin in these neurons. We confirm both predictions, supporting that the energy requirement of Re + ECLII neurons is generally high and that there is a systematic increase in metabolic rate as one moves successively closer to the rhinal fissure. Intriguingly, the systematic variation in energy requirement of the neurons that manifest the observed reelin gradient appears to be consonant with the level of spatial and temporal detail by which they encode information about the external environment.
研究领域:
神经科学
·
分子生物学
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DOI
高影响因子
CELL PROLIFERATION
·
2023
·
IF 8.5
Ning Chen,Shenghui Liu,Dan Qin,Dian Guan,Yaqing Chen,Chenjiao Hou,Songyun Zheng,Liqiang Wang,Xiangmei Chen,Wei Chen,Lisheng Zhang
The activation of hepatic stellate cells (HSCs) is the main cause of liver fibrogenesis in response to different etiologies of chronic liver injuries. HSCs are heterogeneous, but the lack of specific markers to distinguish different HSC subset hinders the development of targeted therapy for liver fibrosis. In this study, we aim to reveal new HSC subsets by cell fate tracking. We constructed a novel ReelinCreERT2 transgenic mouse model to track the fate of cells expressing Reelin and their progeny (Reelin + cells). And we investigated the property of Reelin + cells, such as differentiation and proliferation, in hepatotoxic (carbon tetrachloride; CCl 4 ) or cholestatic (bile duct ligation; BDL) liver injury models by immunohistochemistry. Our study revealed that Reelin + cells were a new HSC subset. In terms of activation, migration, and proliferation, Reelin + HSCs displayed different properties from Desmin + HSCs (total HSCs) in cholestatic liver injury model but shared similar properties to total HSCs in hepatotoxic liver injury model. Besides, we did not find evidence that Reelin + HSCs transdifferentiated into hepatocytes or cholangiocytes through mesenchymal-epithelial transition (MET). In this study, our genetic cell fate tracking data reveal that ReelinCreERT2-labelled cells are a new HSC subset, which provides new insights into targeted therapy for liver fibrosis.
研究领域:
肝病学
·
细胞生物学
·
遗传学
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DOI
PubMed
高影响因子
EMBO Molecular Medicine
·
2025
·
IF 8.3
HuangHaofeng,ZhangMin,HuangEnyu,ZhaoYongfang,LiXiaoyu,QiuPu,LiCairui,TaoJiahua,ZhangYuanqi,LuoLianxiang,NingGuozhu,ChenCeshi,ZhangJingjing
Brain metastasis (BM) remains a significant challenge in breast cancer (BC) management. While conventional metastatic routes primarily involve hematogenous dissemination, emerging evidence suggests that BC cells can also migrate along the abluminal surface of blood vessels, bypassing the blood-brain barrier (BBB). To investigate this phenomenon, we established a zebrafish xenograft model utilizing GFP-labeled MDA-MB-231 cells, allowing real-time observation of BC cell migration along the posterior cerebral veins. Our findings revealed that LRP8, an apolipoprotein E receptor, is upregulated in BC patients with brain metastasis. Functional studies demonstrated that LRP8 knockdown significantly inhibited proliferation, migration, and invasion of triple-negative breast cancer (TNBC) cells both in vitro and in vivo. Mechanistically, LRP8 promotes the activation of CDC42, enhancing filopodia formation and cell motility, a process influenced by the neuronal extracellular matrix protein, Reelin. Furthermore, we demonstrated the therapeutic potential of MEN 10207, a neurokinin-2 receptor antagonist, in inhibiting TNBC cell migration and suppressing BM formation in both zebrafish and mouse models. These findings provide novel insights into the mechanisms underlying extravascular brain dissemination of BC, highlighting the Reelin-LRP8-CDC42 axis as a potential therapeutic target for this devastating complication.
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DOI
PubMed
高影响因子
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