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...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996124003784 |
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| author | Héctor Cañeque-Rufo Teresa Fontán-Baselga Milagros Galán-Llario Agata Zuccaro María Gracia Sánchez-Alonso Esther Gramage María del Pilar Ramos-Álvarez Gonzalo Herradón |
| author_facet | Héctor Cañeque-Rufo Teresa Fontán-Baselga Milagros Galán-Llario Agata Zuccaro María Gracia Sánchez-Alonso Esther Gramage María del Pilar Ramos-Álvarez Gonzalo Herradón |
| author_sort | Héctor Cañeque-Rufo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f7272409ed3347fca820711a804a2aa2 |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-f7272409ed3347fca820711a804a2aa22025-01-24T04:44:37ZengElsevierNeurobiology of Disease1095-953X2025-02-01205106776Pleiotrophin deletion prevents high-fat diet-induced cognitive impairment, glial responses, and alterations of the perineuronal nets in the hippocampusHéctor Cañeque-Rufo0Teresa Fontán-Baselga1Milagros Galán-Llario2Agata Zuccaro3María Gracia Sánchez-Alonso4Esther Gramage5María del Pilar Ramos-Álvarez6Gonzalo Herradón7Department of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Spain; Department of Chemistry and Biochemistry, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, SpainDepartment of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, SpainDepartment of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, SpainDepartment of Chemistry and Biochemistry, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, SpainDepartment of Chemistry and Biochemistry, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, SpainDepartment of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, SpainDepartment of Chemistry and Biochemistry, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, SpainDepartment of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Spain; Corresponding author at: School of Pharmacy, Universidad San Pablo-CEU, Urb. Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain.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.http://www.sciencedirect.com/science/article/pii/S0969996124003784PleiotrophinNeuroinflammationMetabolic syndromePerineuronal netsObesity |
| spellingShingle | Héctor Cañeque-Rufo Teresa Fontán-Baselga Milagros Galán-Llario Agata Zuccaro María Gracia Sánchez-Alonso Esther Gramage María del Pilar Ramos-Álvarez Gonzalo Herradón Pleiotrophin deletion prevents high-fat diet-induced cognitive impairment, glial responses, and alterations of the perineuronal nets in the hippocampus Neurobiology of Disease Pleiotrophin Neuroinflammation Metabolic syndrome Perineuronal nets Obesity |
| title | Pleiotrophin deletion prevents high-fat diet-induced cognitive impairment, glial responses, and alterations of the perineuronal nets in the hippocampus |
| title_full | Pleiotrophin deletion prevents high-fat diet-induced cognitive impairment, glial responses, and alterations of the perineuronal nets in the hippocampus |
| title_fullStr | Pleiotrophin deletion prevents high-fat diet-induced cognitive impairment, glial responses, and alterations of the perineuronal nets in the hippocampus |
| title_full_unstemmed | Pleiotrophin deletion prevents high-fat diet-induced cognitive impairment, glial responses, and alterations of the perineuronal nets in the hippocampus |
| title_short | Pleiotrophin deletion prevents high-fat diet-induced cognitive impairment, glial responses, and alterations of the perineuronal nets in the hippocampus |
| title_sort | pleiotrophin deletion prevents high fat diet induced cognitive impairment glial responses and alterations of the perineuronal nets in the hippocampus |
| topic | Pleiotrophin Neuroinflammation Metabolic syndrome Perineuronal nets Obesity |
| url | http://www.sciencedirect.com/science/article/pii/S0969996124003784 |
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