Anti-Inflammatory Activity of Synaptamide in the Peripheral Nervous System in a Model of Sciatic Nerve Injury

Abstract

N-docosahexaenoylethanolamine (DHEA), or synaptamide, is an endogenous metabolite of docosahexaenoic acid (DHA) that exhibits synaptogenic and neurogenic effects. In our previous studies, synaptamide administration inhibited the neuropathic pain-like behavior and reduced inflammation in the central nervous system following sciatic nerve injury. In the present study, we examine the effect of synaptamide on the peripheral nervous system in a neuropathic pain condition. The dynamics of ionized calcium-binding adapter molecule 1 (iba-1), CD68, CD163, myelin basic protein, and the production of interleukin 1β and 6 within the sciatic nerve, as well as the neuro-glial index and the activity of iba-1, CD163, glial fibrillary acidic protein (GFAP), neuronal NO synthase (nNOS), substance P (SP), activating transcription factor 3 (ATF3) in the dorsal root ganglia (DRG), are studied. According to our results, synaptamide treatment (4 mg/kg/day) (1) decreases the weight-bearing deficit after nerve trauma; (2) enhances the remyelination process in the sciatic nerve; (3) shows anti-inflammatory properties in the peripheral nervous system; (4) decreases the neuro-glial index and GFAP immunoreactivity in the DRG; (5) inhibits nNOS- and SP-ergic activity in the DRG, which might contribute to neuropathic pain attenuation. In general, the current study demonstrates the complex effect of synaptamide on nerve injury, which indicates its high potential for neuropathic pain management.

Synaptamide Ameliorates Hippocampal Neurodegeneration and Glial Activation in Mice with Traumatic Brain Injury

“…Moreover, in the dentate gyrus, the drug increased the number of dendritic spines in the animals without TBI. Our analysis of microglia activity largely explained the neuroprotective effects of synaptamide, which has been confirmed to have anti-inflammatory properties in in vitro and in vivo studies [ 25 , 26 , 27 , 28 ]. Synaptamide is a highly active compound that belongs to the N-acyl ethanolamines of the fatty acids group.…”

“…It is an endogenous metabolite and mediator of the central nervous system. Synaptamide has been found to play a crucial role in neuroprotective mechanisms that are activated in various pathological conditions, including neuropathic pain [ 27 , 28 ] and neuroinflammatory processes in the CNS [ 25 , 26 ]. Using cell cultures of mouse embryonic hippocampus, synaptamide has been shown to stimulate neurite outgrowth, the production of synaptic proteins, and synaptogenesis.…”

“…It is an endogenous metabolite and mediator of the central nervous system. Synaptamide has been found to play a crucial role in neuroprotective mechanisms that are activated in various pathological conditions, including neuropathic pain [27,28] and neuroinflammatory processes in the CNS [25,26].…”

Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110

“…Synaptamide has previously been shown to have a broad spectrum of anti-inflammatory, neuroprotective, and neurogenic properties, making it a promising therapeutic agent for various neurological diseases and injuries. For example, treatment with synaptamide in traumatic brain injury or sciatic nerve chronic constriction injury decreased astrogliosis and immunoreactivity and reduced the levels of inflammatory biomarkers such as glial fibrillary acidic protein (GFAP), S100β, and IL-6 [25][26][27][28]. Synaptamide prevented a lipopolysaccharide (LPS)-mediated increase in the production of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in microglial cells [29].…”

Ultrasonographic contrast and therapeutic effects of hydrogen peroxide- responsive nanoparticles in a rat model with sciatic neuritis

“…Several studies have explored the potential of various anti-in ammatory substances, including endogenous metabolites, phytochemicals, or experimental drugs. Moreover, regulating neuroin ammation and in ammatory cytokines, such as TNF-α, IL-1β, and IL-6, is crucial for nerve recovery and neuroprotection in peripheral nerve injury or neuropathic pain model[68][69][70]…”