Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298-0709, USA.
Alcohol Clin Exp Res. 2010 Mar 1;34(3):493-8. doi: 10.1111/j.1530-0277.2009.01114.x. Epub 2009 Dec 17.
There is growing evidence that deficits in neuronal plasticity account for some of the neurological problems observed in fetal alcohol spectrum disorders (FASD). Recently, we showed that early alcohol exposure results in a permanent impairment in visual cortex ocular dominance (OD) plasticity in a ferret model of FASD. This disruption can be reversed, however, by treating animals with a Phosphodiesterase (PDE) type 1 inhibitor long after the period of alcohol exposure.
Because the mammalian brain presents different types of PDE isoforms we tested here whether inhibition of PDE type 4 also ameliorates the effects of alcohol on OD plasticity.
Ferrets received 3.5 g/Kg alcohol i.p. (25% in saline) or saline as control every other day between postnatal day (P) 10 to P30, which is roughly equivalent to the third trimester equivalent of human gestation. Following a prolonged alcohol-free period (10 to 15 days), ferrets had the lid of the right eye sutured closed for 4 days and were examined for ocular dominance changes at the end of the period of deprivation.
Using in vivo electrophysiology we show that inhibition of PDE4 by rolipram does not restore OD plasticity in alcohol-treated ferrets.
This result suggests that contrary to PDE1, PDE4 inhibition does not play a role in the restoration of OD plasticity in the ferret model of FASD.
越来越多的证据表明，神经元可塑性的缺陷是胎儿酒精谱系障碍（FASD）中观察到的一些神经问题的原因。最近，我们表明，早期酒精暴露会导致 FASD 雪貂模型中视觉皮层眼优势（OD）可塑性的永久性损伤。然而，通过在酒精暴露期后很长时间用磷酸二酯酶（PDE）1 型抑制剂治疗动物，可以逆转这种破坏。
由于哺乳动物大脑存在不同类型的 PDE 同工酶，我们在这里测试了抑制 PDE 4 是否也能改善酒精对 OD 可塑性的影响。
雪貂在出生后第 10 天至第 30 天（相当于人类妊娠的第三个 trimester）期间，每隔一天接受 3.5 g/Kg 的腹腔内酒精（25%在盐水中）或盐水作为对照。在长时间的无酒精期（10 至 15 天）后，将右眼的眼睑缝合关闭 4 天，并在剥夺期结束时检查 OD 变化。
我们通过体内电生理学显示，用 rolipram 抑制 PDE4 并不能恢复酒精处理的雪貂的 OD 可塑性。
这一结果表明，与 PDE1 相反，PDE4 抑制在 FASD 雪貂模型中 OD 可塑性的恢复中不起作用。
