目的:探讨p38丝裂原活化蛋白激酶(MAPK)信号对成年弱视小鼠视皮层可塑性再激活的影响。
方法:反向缝合(RS),环境富集(EE),并联合左侧脑室注射p38MAPK抑制剂(SB203580,SB)或p38MAPK激动剂(盐酸脱氢考基,DHC)用于治疗单眼剥夺(MD)的成年弱视小鼠。视觉水上任务,视觉悬崖测试,使用Flash视觉诱发电位来测量视觉功能。然后,高尔基染色和透射电子显微镜用于评估成年弱视小鼠结构可塑性的重新激活。Westernblot和免疫组化检测ATF2、PSD-95、p38MAPK的表达,和磷酸-p38MAPK在左侧视觉皮层。
结果:干预前各组的视功能无统计学差异。与干预前相比,剥夺眼的视力明显提高,视觉深度感知的障碍得到缓解,在EE+RS中P波振幅和C/I比增加,EE+RS+SB,和EE+RS+DMSO基团,EE+RS+DHC组无明显差异。与EE+RS+DHC组相比,树突棘的密度明显更高,左视觉皮层的突触密度显著增加,活动突触区的长度增加,EE+RS左视皮层突触后密度(PSD)厚度增厚,EE+RS+SB,和EE+RS+DMSO组。而且,在EERSDHC组小鼠的左视皮层中,p-p38MAPK的蛋白表达显着增加,而PSD-95和ATF2的蛋白表达显着降低。
结论:RS和EE干预可改善成年弱视小鼠视功能和视觉皮层突触可塑性。然而,激活p38MAPK通过上调p38MAPK的磷酸化和增加ATF2蛋白表达来阻碍视觉功能的恢复。
To investigate the impact of p38 mitogen-activated protein kinase (MAPK) signaling on reactivating visual cortical plasticity in adult amblyopic mice.
Reverse suture (RS), environment enrichment (EE), and combined with left intracerebroventricular injection of p38 MAPK inhibitor (SB203580, SB) or p38 MAPK agonist (dehydrocorydaline hydrochloride, DHC) were utilized to treat adult amblyopic mice with monocular deprivation (MD). The visual water task, visual cliff test, and Flash visual-evoked potential were used to measure the visual function. Then, Golgi staining and transmission electron microscopy were used to assess the reactivation of structural plasticity in adult amblyopic mice. Western blot and immunohistochemistry detected the expression of ATF2, PSD-95, p38 MAPK, and phospho-p38 MAPK in the left visual cortex.
No statistically significant difference was observed in the visual function in each pre-intervention group. Compared to pre-intervention, the visual acuity of deprived eyes was improved significantly, the impairment of visual depth perception was alleviated, and the P wave amplitude and C/I ratio were increased in the EE + RS, the EE + RS + SB, and the EE + RS + DMSO groups, but no significant difference was detected in the EE + RS + DHC group. Compared to EE + RS + DHC group, the density of dendritic spines was significantly higher, the synaptic density of the left visual cortex increased significantly, the length of the active synaptic zone increased, and the thickness of post-synaptic density (PSD) thickened in the left visual cortex of EE + RS, EE + RS + SB, and EE + RS + DMSO groups. And that, the protein expression of p-p38 MAPK increased while that of PSD-95 and ATF2 decreased significantly in the left visual cortex of the EE + RS + DHC group mice.
RS and EE intervention improved the visual function and synaptic plasticity of the visual cortex in adult amblyopic mice. However, activating p38 MAPK hinders the recovery of visual function by upregulating the phosphorylation of p38 MAPK and decreasing the ATF2 protein expression.