Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains
Abstract
:1. Introduction
2. Results
2.1. Sstr4 Expression in Several Pain- and Mood Regulation-Related Brain Regions
2.2. Sstr4 Is Detectable Both in Nociceptive and Anti-Nociceptive Centers as Well as in Glutamatergic Excitatory Neurons of Brain Regions Involved in Mood Regulation
2.3. Activation of the SST4 Receptor Decreases the Excitability of Layer V Pyramidal Neurons
2.4. SSTR4 mRNA Co-Localizes on VGLUT1-Expressing Pyramidal Neurons in Human Neurosurgical Cortical Tissue Samples
3. Discussion
4. Materials and Methods
4.1. G-Protein Activation Assay
4.2. Samples
4.2.1. Mice
4.2.2. Human Post-Mortem and Neurosurgical Cortical Tissues
4.3. Sample Preparation and Investigational Techniques
4.3.1. Mouse
Real-Time Quantitative RT-qPCR
Perfusion and Tissue Processing for Histological Studies
β-Galactosidase-Specific Immunohistochemistry (β-Gal IHC)
SST4-Specific Immunohistochemistry
RNAscope In Situ Hybridization (ISH) on Mouse Samples
Acute Brain Slice Preparation
In Vitro Electrophysiological Recordings
4.3.2. Human
RT-qPCR on Post-Mortem Human Cortical Tissues
RNAscope ISH on Neurosurgical Cortical Tissue Samples
4.4. Experimental Design and Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
SS | Somatostatin |
SST1-5 | somatostatin receptor subtype 1-5 |
SSTR1-5/Sstr1-5 | gene of somatostatin receptor subtype 1-5 in human/mouse |
Sstr4lacZ/lacZ mice | Sstr4-deficient, lacZ knock-in reporter mice |
GIRK | G protein-coupled inward-rectifying potassium channels |
ISH | In situ hybridization |
β-Gal IHC | β-galactosidase immunostaining |
DRG | Dorsal root ganglia |
TG | Trigeminal ganglia |
PrL | Prelimbic cortex |
MPO | Medial preoptic area of the hypothalamus |
BMA | Basomedial amygdala |
CeC | Core of central amygdala |
BLA | Basolateral amygdala |
S1 | Primary somatosensory cortex |
CA1 | Cornu Ammonis 1 region of hippocampus |
MHb | Medial nucleus of habenula |
VPL | Ventral posterolateral thalamic nucleus |
VLPAG | Ventrolateral periaqueductal gray matter |
RMg | Raphe magnus nucleus |
LC | Locus coeruleus |
Vglut1 | Vesicular glutamate transporter 1 |
Gad1 | Glutamate decarboxylase 1 |
Chat | Choline acetyltransferase |
Rbfox3 | RNA Binding Fox-1 Homolog 3, NeuN |
TH | Tyrosine-hydroxylase |
HPA | Hypothalamus-pituitary-adrenal axis |
DAB | 3,3′-diaminobenzidine |
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Kecskés, A.; Pohóczky, K.; Kecskés, M.; Varga, Z.V.; Kormos, V.; Szőke, É.; Henn-Mike, N.; Fehér, M.; Kun, J.; Gyenesei, A.; Renner, É.; Palkovits, M.; Ferdinandy, P.; Ábrahám, I.M.; Gaszner, B.; Helyes, Z. Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains. Int. J. Mol. Sci. 2020, 21, 7788. https://doi.org/10.3390/ijms21207788
Kecskés A, Pohóczky K, Kecskés M, Varga ZV, Kormos V, Szőke É, Henn-Mike N, Fehér M, Kun J, Gyenesei A, Renner É, Palkovits M, Ferdinandy P, Ábrahám IM, Gaszner B, Helyes Z. Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains. International Journal of Molecular Sciences. 2020; 21(20):7788. https://doi.org/10.3390/ijms21207788
Chicago/Turabian StyleKecskés, Angéla, Krisztina Pohóczky, Miklós Kecskés, Zoltán V. Varga, Viktória Kormos, Éva Szőke, Nóra Henn-Mike, Máté Fehér, József Kun, Attila Gyenesei, Éva Renner, Miklós Palkovits, Péter Ferdinandy, István M. Ábrahám, Balázs Gaszner, and Zsuzsanna Helyes. 2020. "Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains" International Journal of Molecular Sciences 21, no. 20: 7788. https://doi.org/10.3390/ijms21207788