Modulation of Hippocampal Astroglial Activity by Synaptamide in Rats with Neuropathic Pain
The present study demonstrates that synaptamide (N-docosahexaenoylethanolamine), an endogenous metabolite of docosahexaenoic acid, when administered subcutaneously (4 mg/kg/day, 14 days), exhibits analgesic activity and promotes cognitive recovery in the rat sciatic nerve chronic constriction injury...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | Brain Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3425/11/12/1561 |
| _version_ | 1797410765317079040 |
|---|---|
| author | Igor Manzhulo Olga Manzhulo Anna Tyrtyshnaia Arina Ponomarenko Sophia Konovalova Ekaterina Ermolenko Elena Milkina Anna Starinets |
| author_facet | Igor Manzhulo Olga Manzhulo Anna Tyrtyshnaia Arina Ponomarenko Sophia Konovalova Ekaterina Ermolenko Elena Milkina Anna Starinets |
| author_sort | Igor Manzhulo |
| collection | DOAJ |
| description | The present study demonstrates that synaptamide (N-docosahexaenoylethanolamine), an endogenous metabolite of docosahexaenoic acid, when administered subcutaneously (4 mg/kg/day, 14 days), exhibits analgesic activity and promotes cognitive recovery in the rat sciatic nerve chronic constriction injury (CCI) model. We analyzed the dynamics of GFAP-positive astroglia and S100β-positive astroglia activity, the expression of nerve growth factor (NGF), and two subunits of the NMDA receptor (NMDAR1 and NMDAR2A) in the hippocampi of the experimental animals. Hippocampal neurogenesis was evaluated by immunohistochemical detection of DCX. Analysis of N-acylethanolamines in plasma and in the brain was performed using the liquid chromatography-mass spectrometry technique. In vitro and in vivo experiments show that synaptamide (1) reduces cold allodynia, (2) improves working memory and locomotor activity, (3) stabilizes neurogenesis and astroglial activity, (4) enhances the expression of NGF and NMDAR1, (5) increases the concentration of Ca<sup>2+</sup> in astrocytes, and (6) increases the production of N-acylethanolamines. The results of the present study demonstrate that synaptamide affects the activity of hippocampal astroglia, resulting in faster recovery after CCI. |
| first_indexed | 2024-03-09T04:34:57Z |
| format | Article |
| id | doaj.art-74213d87f4f8440daa32c166d7208610 |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-09T04:34:57Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-74213d87f4f8440daa32c166d72086102023-12-03T13:28:57ZengMDPI AGBrain Sciences2076-34252021-11-011112156110.3390/brainsci11121561Modulation of Hippocampal Astroglial Activity by Synaptamide in Rats with Neuropathic PainIgor Manzhulo0Olga Manzhulo1Anna Tyrtyshnaia2Arina Ponomarenko3Sophia Konovalova4Ekaterina Ermolenko5Elena Milkina6Anna Starinets7A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041 Vladivostok, RussiaA.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041 Vladivostok, RussiaA.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041 Vladivostok, RussiaA.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041 Vladivostok, RussiaA.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041 Vladivostok, RussiaA.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041 Vladivostok, RussiaA.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041 Vladivostok, RussiaA.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041 Vladivostok, RussiaThe present study demonstrates that synaptamide (N-docosahexaenoylethanolamine), an endogenous metabolite of docosahexaenoic acid, when administered subcutaneously (4 mg/kg/day, 14 days), exhibits analgesic activity and promotes cognitive recovery in the rat sciatic nerve chronic constriction injury (CCI) model. We analyzed the dynamics of GFAP-positive astroglia and S100β-positive astroglia activity, the expression of nerve growth factor (NGF), and two subunits of the NMDA receptor (NMDAR1 and NMDAR2A) in the hippocampi of the experimental animals. Hippocampal neurogenesis was evaluated by immunohistochemical detection of DCX. Analysis of N-acylethanolamines in plasma and in the brain was performed using the liquid chromatography-mass spectrometry technique. In vitro and in vivo experiments show that synaptamide (1) reduces cold allodynia, (2) improves working memory and locomotor activity, (3) stabilizes neurogenesis and astroglial activity, (4) enhances the expression of NGF and NMDAR1, (5) increases the concentration of Ca<sup>2+</sup> in astrocytes, and (6) increases the production of N-acylethanolamines. The results of the present study demonstrate that synaptamide affects the activity of hippocampal astroglia, resulting in faster recovery after CCI.https://www.mdpi.com/2076-3425/11/12/1561N-docosahexaenoylethanolamineDHEAsynaptamidechronic constriction injuryneuropathic painhippocampus |
| spellingShingle | Igor Manzhulo Olga Manzhulo Anna Tyrtyshnaia Arina Ponomarenko Sophia Konovalova Ekaterina Ermolenko Elena Milkina Anna Starinets Modulation of Hippocampal Astroglial Activity by Synaptamide in Rats with Neuropathic Pain Brain Sciences N-docosahexaenoylethanolamine DHEA synaptamide chronic constriction injury neuropathic pain hippocampus |
| title | Modulation of Hippocampal Astroglial Activity by Synaptamide in Rats with Neuropathic Pain |
| title_full | Modulation of Hippocampal Astroglial Activity by Synaptamide in Rats with Neuropathic Pain |
| title_fullStr | Modulation of Hippocampal Astroglial Activity by Synaptamide in Rats with Neuropathic Pain |
| title_full_unstemmed | Modulation of Hippocampal Astroglial Activity by Synaptamide in Rats with Neuropathic Pain |
| title_short | Modulation of Hippocampal Astroglial Activity by Synaptamide in Rats with Neuropathic Pain |
| title_sort | modulation of hippocampal astroglial activity by synaptamide in rats with neuropathic pain |
| topic | N-docosahexaenoylethanolamine DHEA synaptamide chronic constriction injury neuropathic pain hippocampus |
| url | https://www.mdpi.com/2076-3425/11/12/1561 |
| work_keys_str_mv | AT igormanzhulo modulationofhippocampalastroglialactivitybysynaptamideinratswithneuropathicpain AT olgamanzhulo modulationofhippocampalastroglialactivitybysynaptamideinratswithneuropathicpain AT annatyrtyshnaia modulationofhippocampalastroglialactivitybysynaptamideinratswithneuropathicpain AT arinaponomarenko modulationofhippocampalastroglialactivitybysynaptamideinratswithneuropathicpain AT sophiakonovalova modulationofhippocampalastroglialactivitybysynaptamideinratswithneuropathicpain AT ekaterinaermolenko modulationofhippocampalastroglialactivitybysynaptamideinratswithneuropathicpain AT elenamilkina modulationofhippocampalastroglialactivitybysynaptamideinratswithneuropathicpain AT annastarinets modulationofhippocampalastroglialactivitybysynaptamideinratswithneuropathicpain |