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. 2019 Aug 31;60(4):352-360.
doi: 10.3325/cmj.2019.60.352.

Glutamatergic Activation of A1 and A2 Noradrenergic Neurons in the Rat Brain Stem

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Free PMC article

Glutamatergic Activation of A1 and A2 Noradrenergic Neurons in the Rat Brain Stem

Duygu Gok-Yurtseven et al. Croat Med J. .
Free PMC article

Abstract

Aim: 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.

Methods: 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.

Results: 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.

Conclusion: Our results suggest that noradrenergic neurons are regulated and/or activated by glutamatergic system and that these neurons express functional glutamate receptors.

Figures

Figure 1
Figure 1
Representative c-Fos-positive and c-Fos-negative noradrenergic neurons. The arrow indicates c-Fos positivity (dark-blue) in the nucleus of a tyrosine hydroxylase (TH)-positive (brown) neuron. The arrow-head indicates a representative c-Fos-negative noradrenergic neuron.
Figure 2
Figure 2
Representative images of A1 noradrenergic neurons of the brainstem double-stained for c-Fos and tyrosine hydroxylase (TH). The effect of kainic acid (upper set), α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (middle set), and N-methyl-D-aspartic acid (NMDA) (lower set) is shown. Control groups are shown on the left, the agonist injected groups in the middle, and antagonist-injected groups on the right.
Figure 3
Figure 3
Representative images of A2 noradrenergic neurons of the brainstem double stained for c-Fos and tyrosine hydroxylase (TH). The effect of kainic acid (upper set), α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (middle set), and N-methyl-D-aspartic acid (NMDA) (lower set) is shown. Control groups are shown on the left, the agonist injected groups in the middle, and antagonist-injected groups on the right.
Figure 4
Figure 4
The percentages of c-Fos-positive tyrosine hydroxylase (TH) neurons relative to all TH-positive cells. The figure summarizes the effects of agonists and antagonists when compared with controls. Agonist injections activated significantly more neurons when compared with the control animals. Antagonist injections blocked this activation and the percentage of activated neurons decreased significantly. Asterisk indicates the statistical significance when compared with agonist-injected groups. See Table 1 for actual P values.

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