Occlusion of activity dependent synaptic plasticity by late hypoxic long term potentiation after neonatal intermittent hypoxia.
Occlusion of activity dependent synaptic plasticity by late hypoxic long term potentiation after neonatal intermittent hypoxia.
复制标题
新生儿间歇性缺氧后迟发性缺氧长时程增强对活动依赖性突触可塑性的阻断。
DOI：
10.1016/j.expneurol.2020.113575
复制
发表时间：
2021-03
影响因子：
5.3
通讯作者：
Drobyshevsky A
中科院分区：
文献类型：
--
作者：
Goussakov I;Synowiec S;Aksenov DP;Drobyshevsky A
为了阐明新生儿慢性间歇性缺氧 (IH) 后记忆障碍的机制，我们采用了在出生后 3 至 7 天给予严重 IH 的小鼠模型。由于该模型的先前研究并未证明细胞死亡增加，因此我们的主要假设是 IH 导致海马神经元突触可塑性的功能破坏。海马 CA1 区 IH 期间 Schaffer 侧支刺激诱导的突触反应的体内记录显示，病理性晚期缺氧长期增强 (hLTP) (154%) 持续超过 4 小时，并且可以通过低频刺激 (LFS) 去增强作用逆转，或被 NMDA 和 PKA 抑制剂（MK-801 和 CMIQ）。此外，IH 后四小时，晚期 hLTP 部分阻断了正常生理 LTP (pLTP)。早期和晚期 hLTP 阶段是由神经元去极化和 Ca2+ 流入诱导的，通过锰增强 MRI 确定，并且 AMPA 和 NMDA 介导的电流均增加。这与新生儿 pLTP 的机制一致，也与成人 OGD 体外描述的缺血性 LTP 一致。 IH 后 2 天获得的海马切片上也记录了 pLTP 的减少。每次 IH 疗程前注射 MK-801 可改善这种下降，并通过 LFS 去势作用恢复。 pLTP 的闭塞以及新生儿 hLTP 后观察到的仅 NMDA 沉默突触比例下降可能解释了新生儿 IH 后的长期记忆、行为缺陷以及异常突触发生和修剪。
To elucidate the mechanisms of memory impairment after chronic neonatal intermittent hypoxia (IH), we employed a mice model of severe IH administered at postnatal days 3 to 7. Since prior studies in this model did not demonstrate increased cell death, our primary hypothesis was that IH causes a functional disruption of synaptic plasticity in hippocampal neurons. In vivo recordings of Schaffer collateral stimulation-induced synaptic responses during IH in the CA1 region of the hippocampus revealed pathological late phase hypoxic long term potentiation (hLTP) (154%) that lasted more than four hours and could be reversed by depotentiation with low frequency stimulation (LFS), or abolished by NMDA and PKA inhibitors (MK-801 and CMIQ). Furthermore, late phase hLTP partially occluded normal physiological LTP (pLTP) four hours after IH. Early and late hLTP phases were induced by neuronal depolarization and Ca2+ influx, determined with manganese enhanced MRI, and had increased both AMPA and NMDA – mediated currents. This was consistent with mechanisms of pLTP in neonates and also consistent with ischemic LTP described in vitro with OGD in adults. A decrease of pLTP was also recorded on hippocampal slices obtained 2 days after IH. This decrease was ameliorated by MK-801 injections prior to each IH session and restored by LFS depotentiation. Occlusion of pLTP and the observed decreased proportion of NMDA-only silent synapses after neonatal hLTP may explain long term memory, behavioral deficits and abnormal synaptogenesis and pruning following neonatal IH.
登录
查看更多内容
影响因子：
6.3
作者：
Dietz, Robert M.;Orfila, James E.;Herson, Paco S.
通讯作者：
Herson, Paco S.
影响因子：
64.8
作者：
LIAO, DZ;HESSLER, NA;MALINOW, R
通讯作者：
MALINOW, R
影响因子：
3.5
作者：
Goh JJ;Manahan-Vaughan D
通讯作者：
Manahan-Vaughan D
影响因子：
16.2
作者：
ISAAC, JTR;NICOLL, RA;MALENKA, RC
通讯作者：
MALENKA, RC
影响因子：
64.8
作者：
Durand, GM;Kovalchuk, Y;Konnerth, A
通讯作者：
Konnerth, A