Jafarian Maryam, Modarres Mousavi Sayed Mostafa, Rahimi Sadegh, Ghaderi Pakdel Firuze, Lotfinia Ahmad Ali, Lotfinia Mahmoud, Gorji Ali
Brain and Spinal Cord Injury Research Center, Neurosciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran; Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Brain Res. 2021 Apr 15;1757:147304. doi: 10.1016/j.brainres.2021.147304. Epub 2021 Jan 29.
The present study aimed to investigate the alterations of the GABAergic system in the laterodorsal nucleus (LDN) of the thalamus and the somatosensory cortex (SC) in an experimental model of absence seizure. The effects of pharmacological manipulation of both GABA and GABA receptor subunits in the LDN on the generation of spike-wave discharges (SWD) were evaluated. The experiments were carried out in four groups of both WAG/Rij and Wistar rats with 2 and 6 months of age. The expressions of various GABA receptor subunits were studied in the LDN and SC. Furthermore, recordings of unit activity from the LDN and electrocorticography were simultaneously monitored before, during, and after the application of GABA and GABA antagonists in the LDN. The generation of SWD in the older WAG/Rij rats was associated with significant alterations in the expression of GABARα1, GABARβ3, and GABAR2 subunits in the LDN as well as GABARα1, GABARβ3, GABARγ2, and GABAR2 subunits in the SC. Furthermore, the occurrence of SWD was associated with a significant reduction of gene expression of GABAARα1 and increase of GABAARβ3 in the LDN as well as reduction of GABAARα1, GABAARβ3, GABAARγ2, and GABABR2 in the SC. The microionthophoretic application of the GABA antagonist bicuculline resulted in a significant increase in the population firing rate of LDN neurons as well as the mean number and duration of SWD. The application of the GABA antagonist CGP35348 significantly increased the population firing rate of LDN neurons but decreased the mean number of SWD. Our data indicate the regulatory effect of the GABAergic system of the LDN and SC in absence seizures.
本研究旨在探讨失神发作实验模型中丘脑背外侧核（LDN）和躯体感觉皮层（SC）中γ-氨基丁酸（GABA）能系统的变化。评估了LDN中GABA和GABA受体亚基的药理学操作对棘波放电（SWD）产生的影响。实验在四组2月龄和6月龄的WAG/Rij大鼠和Wistar大鼠中进行。研究了LDN和SC中各种GABA受体亚基的表达。此外，在LDN中应用GABA和GABA拮抗剂之前、期间和之后，同时监测LDN的单位活动记录和脑电图。老年WAG/Rij大鼠中SWD的产生与LDN中GABARα1、GABARβ3和GABAR2亚基以及SC中GABARα1、GABARβ3、GABARγ2和GABAR2亚基表达的显著变化有关。此外，SWD的发生与LDN中GABAARα1基因表达的显著降低和GABAARβ3的增加以及SC中GABAARα1、GABAARβ3、GABAARγ2和GABABR2的降低有关。GABA拮抗剂荷包牡丹碱的微量离子电泳应用导致LDN神经元的群体放电率显著增加以及SWD的平均数量和持续时间增加。GABA拮抗剂CGP35348的应用显著增加了LDN神经元的群体放电率，但减少了SWD的平均数量。我们的数据表明LDN和SC的GABA能系统在失神发作中的调节作用。
