Sadowska G B, Stonestreet B S
Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, RI 02905, United States.
Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, RI 02905, United States.
Neuroscience. 2014 Sep 5;275:248-58. doi: 10.1016/j.neuroscience.2014.05.066. Epub 2014 Jun 11.
Gap junctions facilitate intercellular communication and are important in brain development. Connexins (Cx) comprise a transmembrane protein family that forms gap junctions. Cx-32 is expressed in oligodendrocytes and neurons, Cx-36 in neurons, and Cx-43 in astrocytes. Although single antenatal steroid courses are recommended for fetal lung maturation, multiple courses can be given to women at recurrent risk for premature delivery. We examined the effects of single and multiple glucocorticoid courses on Cx-32, Cx-36, and Cx-43 protein expressions in the fetal cerebral cortex, cerebellum, and spinal cord, and differences in Cx expression among brain regions under basal conditions. In the single-course groups, the ewes received dexamethasone (6 mg) or placebo as four intramuscular injections every 12h over 48 h. In the multiple-course groups, the ewes received the same treatment, once a week for 5 weeks starting at 76-78 days of gestation. Cx were measured by Western immunoblot on brain samples from 105 to 108-day gestation fetuses. A single dexamethasone course was associated with increases (P<0.05) in cerebral cortical and spinal cord Cx-36 and Cx-43 and multiple courses with increases in cerebellar and spinal cord Cx-36, and cerebral cortical and cerebellar Cx-43. Cx-32 did not change. Cx-32 was higher in the cerebellum than cerebral cortex and spinal cord, Cx-36 higher in the spinal cord than cerebellum, and Cx-43 higher in the cerebellum and spinal cord than cerebral cortex during basal conditions. In conclusion, maternal glucocorticoid therapy increases specific Cx, responses to different maternal courses vary among Cx and brain regions, and Cx expression differs among brain regions under basal conditions. Maternal treatment with glucocorticoids differentially modulates Cx in the fetal brain.
缝隙连接促进细胞间通讯,在脑发育过程中起重要作用。连接蛋白(Cx)构成形成缝隙连接的跨膜蛋白家族。Cx-32在少突胶质细胞和神经元中表达,Cx-36在神经元中表达,Cx-43在星形胶质细胞中表达。尽管推荐单次产前类固醇疗程用于胎儿肺成熟,但对于有早产复发风险的女性可给予多次疗程。我们研究了单次和多次糖皮质激素疗程对胎儿大脑皮质、小脑和脊髓中Cx-32、Cx-36和Cx-43蛋白表达的影响,以及基础条件下不同脑区Cx表达的差异。在单次疗程组中,母羊接受地塞米松(6毫克)或安慰剂,每12小时肌肉注射一次,共48小时,分四次注射。在多次疗程组中,母羊从妊娠76 - 78天开始接受相同治疗,每周一次,共5周。通过蛋白质免疫印迹法检测妊娠105至108天胎儿脑样本中的Cx。单次地塞米松疗程与大脑皮质和脊髓中Cx-36和Cx-43增加(P<0.05)相关,多次疗程与小脑和脊髓中Cx-36增加以及大脑皮质和小脑中Cx-43增加相关。Cx-32无变化。基础条件下,小脑的Cx-32高于大脑皮质和脊髓,脊髓的Cx-36高于小脑,小脑和脊髓的Cx-43高于大脑皮质。总之,母体糖皮质激素治疗可增加特定的Cx,不同母体疗程的反应在Cx和脑区之间存在差异,基础条件下不同脑区的Cx表达也不同。母体糖皮质激素治疗对胎儿脑内的Cx有不同的调节作用。