The Expression of the Endocannabinoid Receptors CB2 and GPR55 Is Highly Increased during the Progression of Alzheimer’s Disease in <i>App<sup>NL-G-F</sup></i> Knock-In Mice
Background: The endocannabinoid system (ECS) and associated lipid transmitter-based signaling systems play an important role in modulating brain neuroinflammation. ECS is affected in neurodegenerative disorders, such as Alzheimer’s disease (AD). Here we have evaluated the non-psychotropic endocannab...
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MDPI AG
2023-05-01
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| author | Dina Medina-Vera Hongjing Zhao Erika Bereczki Cristina Rosell-Valle Makoto Shimozawa Gefei Chen Fernando Rodríguez de Fonseca Per Nilsson Simone Tambaro |
| author_facet | Dina Medina-Vera Hongjing Zhao Erika Bereczki Cristina Rosell-Valle Makoto Shimozawa Gefei Chen Fernando Rodríguez de Fonseca Per Nilsson Simone Tambaro |
| author_sort | Dina Medina-Vera |
| collection | DOAJ |
| description | Background: The endocannabinoid system (ECS) and associated lipid transmitter-based signaling systems play an important role in modulating brain neuroinflammation. ECS is affected in neurodegenerative disorders, such as Alzheimer’s disease (AD). Here we have evaluated the non-psychotropic endocannabinoid receptor type 2 (CB2) and lysophosphatidylinositol G-protein-coupled receptor 55 (GPR55) localization and expression during Aβ-pathology progression. Methods: Hippocampal gene expression of CB2 and GPR55 was explored by qPCR analysis, and brain distribution was evaluated by immunofluorescence in the wild type (WT) and APP knock-in <i>App<sup>NL-G-F</sup></i> AD mouse model. Furthermore, the effects of Aβ42 on CB2 and GPR55 expression were assessed in primary cell cultures. Results: CB2 and GPR55 mRNA levels were significantly upregulated in <i>App<sup>NL-G-F</sup></i> mice at 6 and 12 months of age, compared to WT. CB2 was highly expressed in the microglia and astrocytes surrounding the Aβ plaques. Differently, GPR55 staining was mainly detected in neurons and microglia but not in astrocytes. In vitro, Aβ42 treatment enhanced CB2 receptor expression mainly in astrocytes and microglia cells, whereas GPR55 expression was enhanced primarily in neurons. Conclusions: These data show that Aβ pathology progression, particularly Aβ42, plays a crucial role in increasing the expression of CB2 and GPR55 receptors, supporting CB2 and GPR55 implications in AD. |
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| language | English |
| last_indexed | 2024-03-11T02:44:56Z |
| publishDate | 2023-05-01 |
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| series | Biology |
| spelling | doaj.art-97e68dfdb67d4382b3c85ca13d2c9f522023-11-18T09:22:49ZengMDPI AGBiology2079-77372023-05-0112680510.3390/biology12060805The Expression of the Endocannabinoid Receptors CB2 and GPR55 Is Highly Increased during the Progression of Alzheimer’s Disease in <i>App<sup>NL-G-F</sup></i> Knock-In MiceDina Medina-Vera0Hongjing Zhao1Erika Bereczki2Cristina Rosell-Valle3Makoto Shimozawa4Gefei Chen5Fernando Rodríguez de Fonseca6Per Nilsson7Simone Tambaro8Instituto de Investigación Biomédica de Málaga-IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, 29010 Málaga, SpainCollege of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, ChinaDepartment of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, 17164 Solna, SwedenInstituto de Investigación Biomédica de Málaga-IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, 29010 Málaga, SpainDepartment of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, 17164 Solna, SwedenDepartment of Biosciences and Nutrition, Karolinska Institutet, 14152 Huddinge, SwedenInstituto de Investigación Biomédica de Málaga-IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, 29010 Málaga, SpainDepartment of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, 17164 Solna, SwedenDepartment of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, 17164 Solna, SwedenBackground: The endocannabinoid system (ECS) and associated lipid transmitter-based signaling systems play an important role in modulating brain neuroinflammation. ECS is affected in neurodegenerative disorders, such as Alzheimer’s disease (AD). Here we have evaluated the non-psychotropic endocannabinoid receptor type 2 (CB2) and lysophosphatidylinositol G-protein-coupled receptor 55 (GPR55) localization and expression during Aβ-pathology progression. Methods: Hippocampal gene expression of CB2 and GPR55 was explored by qPCR analysis, and brain distribution was evaluated by immunofluorescence in the wild type (WT) and APP knock-in <i>App<sup>NL-G-F</sup></i> AD mouse model. Furthermore, the effects of Aβ42 on CB2 and GPR55 expression were assessed in primary cell cultures. Results: CB2 and GPR55 mRNA levels were significantly upregulated in <i>App<sup>NL-G-F</sup></i> mice at 6 and 12 months of age, compared to WT. CB2 was highly expressed in the microglia and astrocytes surrounding the Aβ plaques. Differently, GPR55 staining was mainly detected in neurons and microglia but not in astrocytes. In vitro, Aβ42 treatment enhanced CB2 receptor expression mainly in astrocytes and microglia cells, whereas GPR55 expression was enhanced primarily in neurons. Conclusions: These data show that Aβ pathology progression, particularly Aβ42, plays a crucial role in increasing the expression of CB2 and GPR55 receptors, supporting CB2 and GPR55 implications in AD.https://www.mdpi.com/2079-7737/12/6/805endocannabinoid systemcannabinoid receptorsCB2GPR55neuroinflammationAPP knock-in mice |
| spellingShingle | Dina Medina-Vera Hongjing Zhao Erika Bereczki Cristina Rosell-Valle Makoto Shimozawa Gefei Chen Fernando Rodríguez de Fonseca Per Nilsson Simone Tambaro The Expression of the Endocannabinoid Receptors CB2 and GPR55 Is Highly Increased during the Progression of Alzheimer’s Disease in <i>App<sup>NL-G-F</sup></i> Knock-In Mice Biology endocannabinoid system cannabinoid receptors CB2 GPR55 neuroinflammation APP knock-in mice |
| title | The Expression of the Endocannabinoid Receptors CB2 and GPR55 Is Highly Increased during the Progression of Alzheimer’s Disease in <i>App<sup>NL-G-F</sup></i> Knock-In Mice |
| title_full | The Expression of the Endocannabinoid Receptors CB2 and GPR55 Is Highly Increased during the Progression of Alzheimer’s Disease in <i>App<sup>NL-G-F</sup></i> Knock-In Mice |
| title_fullStr | The Expression of the Endocannabinoid Receptors CB2 and GPR55 Is Highly Increased during the Progression of Alzheimer’s Disease in <i>App<sup>NL-G-F</sup></i> Knock-In Mice |
| title_full_unstemmed | The Expression of the Endocannabinoid Receptors CB2 and GPR55 Is Highly Increased during the Progression of Alzheimer’s Disease in <i>App<sup>NL-G-F</sup></i> Knock-In Mice |
| title_short | The Expression of the Endocannabinoid Receptors CB2 and GPR55 Is Highly Increased during the Progression of Alzheimer’s Disease in <i>App<sup>NL-G-F</sup></i> Knock-In Mice |
| title_sort | expression of the endocannabinoid receptors cb2 and gpr55 is highly increased during the progression of alzheimer s disease in i app sup nl g f sup i knock in mice |
| topic | endocannabinoid system cannabinoid receptors CB2 GPR55 neuroinflammation APP knock-in mice |
| url | https://www.mdpi.com/2079-7737/12/6/805 |
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