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...

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Bibliographic Details
Published in:Brain sciences 2021-11, Vol.11 (12), p.1561
Main Authors: Manzhulo, Igor, Manzhulo, Olga, Tyrtyshnaia, Anna, Ponomarenko, Arina, Konovalova, Sophia, Ermolenko, Ekaterina, Milkina, Elena, Starinets, Anna
Format: Article
Language:English
Subjects:
Analgesics
Animals
Astrocytes
chronic constriction injury
Cognitive ability
Cold
Cytokines
DHEA
Docosahexaenoic acid
Doublecortin protein
Glial fibrillary acidic protein
Glutamic acid receptors
Glutamic acid receptors (ionotropic)
Hippocampus
Liquid chromatography
Locomotor activity
Mass spectroscopy
Memory
N-docosahexaenoylethanolamine
N-Methyl-D-aspartic acid receptors
Nerve growth factor
Nervous system
Neuralgia
Neurogenesis
neuropathic pain
Ostomy
Pain
Pain perception
Sciatic nerve
Short term memory
synaptamide
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Summary: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 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.
ISSN:2076-3425
2076-3425
DOI:10.3390/brainsci11121561