胍丁胺
神经科学
丙戊酸
谷氨酸的
前额叶皮质
自闭症谱系障碍
自闭症
心理学
兴奋性突触后电位
海马体
NMDA受体
动物研究
谷氨酸受体
抑制性突触后电位
医学
癫痫
认知
生物
受体
精神科
内科学
氨基酸
精氨酸
生物化学
作者
Ji Woon Kim,Hana Seung,Ki Chan Kim,Edson Luck Gonzales,Hyun‐A Oh,Sung Min Yang,Mee Jung Ko,Seol‐Heui Han,Sourav Banerjee,Chan Young Shin
标识
DOI:10.1016/j.neuropharm.2016.09.014
摘要
Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. Interestingly, our previous study involving the valproic acid animal model of autism (VPA animal model) has demonstrated excitatory-inhibitory imbalance (E/I imbalance) due to enhanced differentiation of glutamatergic neurons and reduced GABAergic neurons. Here, we investigated the potential of agmatine, an endogenous NMDA receptor antagonist, as a novel therapeutic candidate in ameliorating ASD symptoms by modulating E/I imbalance using the VPA animal model. We observed that a single treatment of agmatine rescued the impaired social behaviors as well as hyperactive and repetitive behaviors in the VPA animal model. We also observed that agmatine treatment rescued the overly activated ERK1/2 signaling in the prefrontal cortex and hippocampus of VPA animal models, possibly, by modulating over-excitability due to enhanced excitatory neural circuit. Taken together, our results have provided experimental evidence suggesting a possible therapeutic role of agmatine in ameliorating ASD-like symptoms in the VPA animal model of ASD.
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