N-Docosahexaenoylethanolamine Attenuates Neuroinflammation and Improves Hippocampal Neurogenesis in Rats with Sciatic Nerve Chronic Constriction Injury

Abstract

Chronic neuropathic pain is a condition that causes both sensory disturbances and a variety of functional disorders, indicating the involvement of various brain structures in pain pathogenesis. One of the factors underlying chronic neuropathic pain is neuroinflammation, which is accompanied by microglial activation and pro-inflammatory factor release. N-docosahexaenoylethanolamine (DHEA, synaptamide) is an endocannabinoid-like metabolite synthesized endogenously from docosahexaenoic acid. Synaptamide exhibits anti-inflammatory activity and improves neurite outgrowth, neurogenesis, and synaptogenesis within the hippocampus. This study aims to evaluate the effects of synaptamide obtained by the chemical modification of DHA, extracted from the Far Eastern raw material Berryteuthis magister on neuroinflammatory response and hippocampal neurogenesis changes during neuropathic pain. The study of microglial protein and cytokine concentrations was performed using immunohistochemistry and ELISA. The brain lipid analysis was performed using the liquid chromatography-mass spectrometry technique. Behavioral experiments showed that synaptamide prevented neuropathic pain-associated sensory and behavioral changes, such as thermal allodynia, impaired locomotor activity, working and long-term memory, and increased anxiety. Synaptamide attenuated microglial activation, release of proinflammatory cytokines, and decrease in hippocampal neurogenesis. Lipid analysis revealed changes in the brain N-acylethanolamines composition and plasmalogen concentration after synaptamide administration. In conclusion, we show here that synaptamide may have potential for use in preventing or treating neuropathic cognitive pain and emotional effects.

N-docosahexaenoylethanolamine reduces neuroinflammation and cognitive impairment after mild traumatic brain injury in rats

“…DHEA dosage was chosen using the literature data and our previously obtained results. To date, there is no data on the use of DHEA in TBI, however, it is known that DHEA at a concentration of 10 mg/kg has an antinociceptive effect in mice 36 , 37 . In addition, in previous DHEA studies in a model of LPS-induced inflammation in mice a dosage of 2 to 10 mg/kg was used 33 , 38 .…”

“…Assessment of neurological function. Gross neurological motor function was evaluated using a neurological severity score 37 . The NSS is derived from a 9-item checklist assessing: monoparesis/hemiparesis, exit circle, startle reflex, inability to walk straight and seeking behavior.…”

N-Docosahexanoylethanolamine Reduces Microglial Activation and Improves Hippocampal Plasticity in a Murine Model of Neuroinflammation

“…Synaptamide administration decreased lipopolysaccharide (LPS)-mediated microglial activation and expression of pro-inflammatory cytokines, chemokines, and iNOS in rat brains. In addition, the anti-inflammatory and analgesic activity of synaptamide in vivo was shown in a study on a rat model of sciatic nerve chronic constriction injury [ 29 ]. DHA has a similar activity [ 30 , 31 , 32 ]; however, it is assumed that synaptamide has an activity ten times higher than that of DHA [ 19 , 21 ].…”

Involvement of Microglia in Neurodegenerative Diseases: Beneficial Effects of Docosahexahenoic Acid (DHA) Supplied by Food or Combined with Nanoparticles

“…Furthermore, more doublecortin-positive neurons and proliferating cell nuclear-positive cells have been counted in the dentate gyrus subgranular zone in the CCI synaptamide treated rats compared to the CCI rats. Behavioral improvements were also observed in the synaptamide-treated groups [ 45 ].…”