Synaptamide Modulates Astroglial Activity in Mild Traumatic Brain Injury

Abstract

At present, the study of the neurotropic activity of polyunsaturated fatty acid ethanolamides (N-acylethanolamines) is becoming increasingly important. N-docosahexaenoylethanolamine (synaptamide, DHEA) is a highly active metabolite of docosahexaenoic acid (DHA) with neuroprotective, synaptogenic, neuritogenic, and anti-inflammatory properties in the nervous system. Synaptamide tested in the present study was obtained using a chemical modification of DHA isolated from squid Berryteuthis magister liver. The results of this study demonstrate the effects of synaptamide on the astroglial response to injury in the acute (1 day) and chronic (7 days) phases of mild traumatic brain injury (mTBI) development. HPLC-MS study revealed several times increase of synaptamide concentration in the cerebral cortex and serum of experimental animals after subcutaneous administration (10 mg/kg/day). Using immunohistochemistry, it was shown that synaptamide regulates the activation of GFAP- and S100β-positive astroglia, reduce nNOS-positive immunostaining, and stimulates the secretion of neurotrophin BDNF. Dynamics of superoxide dismutase production in synaptamide treatment confirm the antioxidant efficacy of the test compound. We found a decrease in TBI biomarkers such as GFAP, S100β, and IL-6 in the blood serum of synaptamide-treated experimental animals using Western blot analysis. The results indicate the high therapeutic potential of synaptamide in reducing the severity of the brain damage consequences.

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].…”