多营养蛋白缺失可防止高脂肪饮食引起的认知障碍、神经胶质反应和海马神经元周围网的改变。

IF 5.1 2区 医学 Q1 NEUROSCIENCES
Héctor Cañeque-Rufo , Teresa Fontán-Baselga , Milagros Galán-Llario , Agata Zuccaro , María Gracia Sánchez-Alonso , Esther Gramage , María del Pilar Ramos-Álvarez , Gonzalo Herradón
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引用次数: 0

摘要

肥胖和代谢紊乱,如代谢综合征(MetS)促进神经退行性疾病和认知能力下降的发展。持续的神经炎症在这一过程中起着重要作用。多营养蛋白(PTN)是一种调节能量代谢和高脂肪饮食(HFD)诱导的神经炎症的细胞因子,这表明PTN可能在肥胖和大脑改变(包括认知能力下降)之间的联系中发挥重要作用。为了验证这一假设,我们在Ptn基因缺陷小鼠(Ptn-/-)中使用了hfd诱导的肥胖模型。首先,我们证实Ptn缺失可以防止hfd诱导的肥胖。我们的研究结果表明,用HFD喂养野生型(Ptn+/+)小鼠6个月会导致新物体识别任务中的短期和长期记忆丧失。令人惊讶的是,在喂食HFD的Ptn-/-小鼠中,我们没有观察到任何认知障碍的迹象。此外,我们观察到HFD诱导Ptn+/+小鼠的小胶质细胞反应、星形胶质细胞消耗和神经周围网(PNNs)改变,而HFD在Ptn-/-小鼠中大多被阻止了这些影响。这些结果表明PTN在HFD诱导的代谢反应和脑改变中起着至关重要的作用,并表明PTN信号通路是与MetS相关的脑疾病的有希望的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pleiotrophin deletion prevents high-fat diet-induced cognitive impairment, glial responses, and alterations of the perineuronal nets in the hippocampus
Obesity and metabolic disorders, such as metabolic syndrome (MetS) facilitate the development of neurodegenerative diseases and cognitive decline. Persistent neuroinflammation plays an important role in this process. Pleiotrophin (PTN) is a cytokine that regulates energy metabolism and high-fat diet (HFD)-induced neuroinflammation, suggesting that PTN could play an important role in the connection between obesity and brain alterations, including cognitive decline. To test this hypothesis, we used an HFD-induced obesity model in Ptn genetically deficient mice (Ptn−/−). First, we confirmed that Ptn deletion prevents HFD-induced obesity. Our findings demonstrate that feeding wild-type (Ptn+/+) mice with HFD for 6 months results in short- and long-term memory loss in the novel object recognition task. Surprisingly, we did not observe any sign of cognitive impairment in Ptn−/− mice fed with HFD. In addition, we observed that HFD induced microglial responses, astrocyte depletion, and perineuronal nets (PNNs) alterations in Ptn+/+ mice, while these effects of HFD were mostly prevented in Ptn−/− mice. These results show a crucial role of PTN in metabolic responses and brain alterations induced by HFD and suggest the PTN signalling pathway as a promising therapeutic target for brain disorders associated with MetS.
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来源期刊
Neurobiology of Disease
Neurobiology of Disease 医学-神经科学
CiteScore
11.20
自引率
3.30%
发文量
270
审稿时长
76 days
期刊介绍: Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.
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