Long C J, Butler S, Fesi J, Frank C, Canning D A, Zderic S A
John W. Duckett Center for Pediatric Urology at The Children's Hospital of Philadelphia, USA; The Perelman School of Medicine at The University of Pennsylvania, USA.
John W. Duckett Center for Pediatric Urology at The Children's Hospital of Philadelphia, USA.
J Pediatr Urol. 2014 Aug;10(4):598-604. doi: 10.1016/j.jpurol.2014.04.002. Epub 2014 Apr 24.
Social stress can suppress the voiding reflex, with resultant diminished voiding frequency and increased volumes. The calcineurin-NFAT (nuclear factor of activated T cells) pathway is important in memory development. It was hypothesized that interruption of the calcineurin-NFAT pathway might prevent social stress-induced voiding dysfunction.
Mice were subjected to social stress in an established resident-intruder model for 1 h, followed by 23 h of barrier separation. NFATc3, NFATc4 knockout (KO) and wild-type (WT) mice were studied. At two weeks, voiding patterns were collected; this was followed by sacrifice. Corticotropin-releasing factor (CRF) mRNA expression in Barrington's nucleus (BN) was determined by in-situ hybridization.
Social stress decreased voiding frequency and increased voided volumes in WT strains. At baseline, NFATc3 KO mice showed decreased voids and increased volumes, while the NFATc4 KO mice resisted social stress. However, CRF mRNA increased in WT mice following social stress and was increased at baseline in NFATc3 KO mice. It was found that CRF mRNA did not increase following social stress in NFATc4 KO mice. The administration of CsA to WT mice normalized voiding patterns following social stress, albeit with no effect on CRF mRNA in BN.
Disrupting the calcineurin-NFAT axis by either genetic or pharmacologic approaches confers resistance to the development of social stress-induced voiding and dysfunction.
社会压力可抑制排尿反射，导致排尿频率降低和尿量增加。钙调神经磷酸酶 - 活化T细胞核因子（NFAT）通路在记忆发育中起重要作用。据推测，中断钙调神经磷酸酶 - NFAT通路可能预防社会压力诱导的排尿功能障碍。
在既定的定居者 - 入侵者模型中，让小鼠承受1小时的社会压力，随后进行23小时的屏障隔离。对NFATc3、NFATc4基因敲除（KO）小鼠和野生型（WT）小鼠进行研究。两周时，收集排尿模式；之后进行处死。通过原位杂交测定巴林顿核（BN）中促肾上腺皮质激素释放因子（CRF）mRNA的表达。
社会压力使WT品系小鼠的排尿频率降低，尿量增加。在基线时，NFATc3 KO小鼠排尿次数减少，尿量增加，而NFATc4 KO小鼠抵抗社会压力。然而，社会压力后WT小鼠的CRF mRNA增加，NFATc3 KO小鼠在基线时CRF mRNA就增加。发现社会压力后NFATc4 KO小鼠的CRF mRNA未增加。给WT小鼠注射环孢素A可使社会压力后的排尿模式正常化，尽管对BN中的CRF mRNA无影响。
通过遗传或药理学方法破坏钙调神经磷酸酶 - NFAT轴可使小鼠对社会压力诱导的排尿及功能障碍的发生产生抗性。
