Gok-Yurtseven Duygu, Kafa Ilker M, Minbay Zehra, Eyigor Ozhan
Ozhan Eyigor, Bursa Uludağ University Faculty of Medicine, Department of Histology and Embryology, University Ave. No:101, Gorukle, Bursa, Turkey,
Croat Med J. 2019 Aug 31;60(4):352-360. doi: 10.3325/cmj.2019.60.352.
To analyze the effects of glutamatergic agonists and antagonists on the activation of the A1 and A2 noradrenergic neurons localized in caudal ventrolateral medulla and nucleus tractus solitarii, respectively.
Rats were injected with glutamatergic agonists - kainic acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or N-methyl-D-aspartic acid (NMDA), and the brain sections were prepared for immunohistochemistry. Before agonist injections, antagonists - 6-cyano-7-nitroquinoxaline-2,3-dione or dizocilpine were administered. The expression of c-Fos, as the neuronal activation marker, and tyrosine hydroxylase (TH), as the marker of noradrenergic neurons was assessed with dual immunohistochemistry. The percentage of c-Fos-positive noradrenergic neurons relative to all TH-positive neurons in the respective areas of the brain stem was calculated.
All three glutamatergic agonists significantly increased the number of the c-Fos-positive noradrenergic neurons in both the A1 and A2 area when compared with control animals. Kainic acid injection activated about 57% of TH-positive neurons in A1 and 40% in A2, AMPA activated 26% in A1 and 38% in A2, and NMDA 77% in A1 and 22% in A2. The injections of appropriate glutamatergic antagonists greatly decreased the number of activated noradrenergic neurons.
Our results suggest that noradrenergic neurons are regulated and/or activated by glutamatergic system and that these neurons express functional glutamate receptors.
分析谷氨酸能激动剂和拮抗剂对分别位于延髓尾端腹外侧和孤束核的A1和A2去甲肾上腺素能神经元激活的影响。
给大鼠注射谷氨酸能激动剂—— kainic酸、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）或N-甲基-D-天冬氨酸（NMDA），并制备脑切片用于免疫组织化学。在注射激动剂之前，给予拮抗剂——6-氰基-7-硝基喹喔啉-2,3-二酮或地佐环平。用双重免疫组织化学评估作为神经元激活标志物的c-Fos的表达以及作为去甲肾上腺素能神经元标志物的酪氨酸羟化酶（TH）的表达。计算脑干各区域中c-Fos阳性去甲肾上腺素能神经元相对于所有TH阳性神经元的百分比。
与对照动物相比，所有三种谷氨酸能激动剂均显著增加了A1和A2区域中c-Fos阳性去甲肾上腺素能神经元的数量。注射kainic酸激活了A1中约57%的TH阳性神经元和A2中40%的TH阳性神经元，注射AMPA激活了A1中26%的TH阳性神经元和A2中38%的TH阳性神经元，注射NMDA激活了A1中77%的TH阳性神经元和A2中22%的TH阳性神经元。注射适当的谷氨酸能拮抗剂大大减少了激活的去甲肾上腺素能神经元的数量。
我们的结果表明，去甲肾上腺素能神经元受谷氨酸能系统调节和/或激活，并且这些神经元表达功能性谷氨酸受体。
