Synaptamide (Dehydroepiandrosteron(DHEA)) is an endogenous GPR110 (ADGRF1) ligand that stimulates cAMP production with an EC50 value of 1.27nM[1]. By binding to GPR110, Synaptamide activates Gαs protein, increases cAMP, promotes neurogenesis, neurite growth, and synaptogenesis[2]. Synaptamide has been widely used in animal models of brain injury to improve neurological function and inhibit neuroinflammation[3].
In vitro, Synaptamide treatment at 10μM in SIM-A9 cells for 24 hours can reverse the morphological changes of cell induced by lipopolysaccharide and reduce the production of IL-1β and IL-6 induced by lipopolysaccharide[4]. Treatment of rat primary astrocytes with 10μM Synaptamide for 48 hours significantly increased the activity of superoxide dismutase (SOD), without altering the cell morphology[5]. Treatment of rat neural stem cells (NSCs) with 10 nM Synaptamide for 72 hours can reverse the inhibitory effect of 50 mM ethanol on cell differentiation, and also prevent the reduction in Tuj-1 expression and the decrease in phosphorylation levels of PKA and CREB caused by ethanol exposure[6].
In vivo, Synaptamide treatment via subcutaneous injection at a dose of 10mg/kg/day for 7 consecutive days can improve brain function in a traumatic brain injury (TBI) mouse model, alter the morphology of neurons, and reduce inflammation in the cortex[7]. For one week, 10mg/kg/day doses of Synaptamide were administered subcutaneously to reduce the serum levels of inflammatory factors in the TBI rat model, regulate the activation of GFAP and S100β positive astrocytes, decrease nNOS positive immunostaining, and stimulate the secretion of neurotrophic factors[8].
References:
[1] Chen H, Kevala K, Aflaki E, et al. GPR110 ligands reduce chronic optic tract gliosis and visual deficit following repetitive mild traumatic brain injury in mice[J]. Journal of neuroinflammation, 2021, 18(1): 157.
[2] Kim H Y, Huang B X, Spector A A. Molecular and signaling mechanisms for docosahexaenoic acid-derived neurodevelopment and neuroprotection[J]. International Journal of Molecular Sciences, 2022, 23(9): 4635.
[3] Tyrtyshnaia A, Manzhulo O, Manzhulo I. Synaptamide ameliorates hippocampal neurodegeneration and glial activation in mice with traumatic brain injury[J]. International Journal of Molecular Sciences, 2023, 24(12): 10014.
[4] Ponomarenko A I, Tyrtyshnaia A A, Pislyagin E A, et al. N-docosahexaenoylethanolamine reduces neuroinflammation and cognitive impairment after mild traumatic brain injury in rats[J]. Scientific Reports, 2021, 11(1): 756.
[5] Starinets A, Tyrtyshnaia A, Kipryushina Y, et al. Analgesic Activity of Synaptamide in a Rat Sciatic Nerve Chronic Constriction Injury Model[J]. Cells Tissues Organs, 2022, 211(1): 73-84.
[6] Rashid M A, Kim H Y. N-Docosahexaenoylethanolamine ameliorates ethanol-induced impairment of neural stem cell neurogenic differentiation[J]. Neuropharmacology, 2016, 102: 174-185.
[7] Manzhulo I, Tyrtyshnaia A, Egoraeva A, et al. Anti-inflammatory and anti-apoptotic activity of synaptamide improves the morphological state of neurons in traumatic brain injury[J]. Neuropharmacology, 2024, 258: 110094.
[8] Ponomarenko A, Tyrtyshnaia A, Ivashkevich D, et al. Synaptamide modulates astroglial activity in mild traumatic brain injury[J]. Marine Drugs, 2022, 20(8): 538.
Synaptamide (Dehydroepiandrosteron(DHEA))是一种内源性GPR110（ADGRF1）配体，可刺激cAMP生成，EC50值为1.27nM[1]。Synaptamide通过结合GPR110激活Gαs蛋白，提高cAMP水平，进而促进神经发生、神经突生长和突触形成[2]。Synaptamide已广泛应用于脑损伤动物模型中以改善神经功能并抑制神经炎症[3]。
在体外，使用10μM的Synaptamide处理SIM-A9细胞24小时，可逆转脂多糖诱导的细胞形态改变，并减少IL-1β和IL-6的产生[4]。用10μM的Synaptamide处理大鼠原代星形胶质细胞48小时，能显著提高超氧化物歧化酶活性，且不改变细胞形态[5]。以10nM的Synaptamide处理大鼠神经干细胞(NSCs)72小时，可逆转50mM乙醇对细胞分化的抑制作用，并阻止乙醇暴露引起的Tuj-1表达下降及PKA和CREB磷酸化水平降低[6]。
在体内，连续7天每日皮下注射10mg/kg/day剂量的Synaptamide，能改善创伤性脑损伤(TBI)小鼠模型的大脑功能，改变神经元形态，并减轻皮层炎症反应[7]。在TBI大鼠模型中，连续一周每日皮下注射10mg/kg剂量的Synaptamide，可降低血清炎症因子水平，调节GFAP和S100β阳性星形胶质细胞的活化，减少nNOS阳性免疫染色，并刺激神经营养因子的分泌[8]。