Upregulation of the mGlu5 receptor and COX-2 protein in the mouse brain after imipramine and NS398, searching for mechanisms of regulation
| Autor: | Katarzyna Stachowicz, Patrycja Patrycja Pańczyszyn-Trzewik, Szymon Rzeźniczek, Tomasz Lenda, Magdalena Sowa-Kućma, Paulina Misztak |
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| Přispěvatelé: | Stachowicz, K, Misztak, P, Pańczyszyn-Trzewik, P, Lenda, T, Rzeźniczek, S, Sowa-Kućma, M |
| Rok vydání: | 2021 |
| Předmět: |
Male
Imipramine Receptor Metabotropic Glutamate 5 Antidepressive Agents Tricyclic Neurotransmission Pharmacology GABA Mice Cellular and Molecular Neuroscience Phospholipase A2 Downregulation and upregulation medicine Animals Cyclooxygenase Inhibitors NS398 Receptor Nitrobenzenes Sulfonamides Adrenergic Uptake Inhibitors biology Chemistry Glutamate receptor Brain Cell Biology COX-2 Endocannabinoid system Up-Regulation Mice Inbred C57BL mGlu5 receptor Cyclooxygenase 2 Metabotropic glutamate receptor biology.protein Glutamate medicine.drug |
| Zdroj: | Neurochemistry International. 150:105193 |
| ISSN: | 0197-0186 |
| DOI: | 10.1016/j.neuint.2021.105193 |
| Popis: | Imipramine belongs to a group of tricyclic antidepressants (TCAs). It has been also documented that its antidepressant activity connects with the modulation of cytosolic phospholipase A2 (cPLA2) and arachidonic acid (AA) turnover. Through this mechanism, imipramine can indirectly modify glutamate (Glu) transmission. Additionally, it has been shown that chronic treatment with imipramine results in the upregulation of the metabotropic glutamate receptor subtype 5 (mGlu5 receptor) in the hippocampus of rats. Our previous study revealed that manipulation of the AA pathway via inhibition of cyclooxygenase-2 (COX-2) by selective COX-2 inhibitor (NS398) could effectively modulate the behavior of mice treated with imipramine. Here, we hypothesized that COX-2 inhibition could similarly to imipramine influence mGlu5 receptor, and thus NS398 can modulate the effect of imipramine on Glu. Moreover, such regulation changes should correspond with alterations in neurotransmission. Increased cPLA activity after imipramine administration may change the activity of the AA pathway and the endocannabinoid metabolism, e.g., 2-Arachidonyl-glycerol (2-AG). To verify the idea, mGlu5 receptor level was investigated in the hippocampus (HC) and prefrontal cortex (PFC) of mice treated for 7 or 14 days with imipramine and/or COX-2 inhibitor: NS398. Western blot and PCR analyses were conducted. Moreover, the excitatory (Glu) and inhibitory (gamma-aminobutyric acid; GABA) neurotransmitters were measured using HPLC and 2-AG using ELISA. A time-dependent change in mGlu5 receptor and COX-2 protein level, COX-2 expression, and 2-AG level in the PFC after imipramine administration was found. Up-regulation of mGlu5 receptor after NS398 was found in HC and PFC. A structure-dependent shift between excitatory vs. inhibitory transmission was detected when NS398 and imipramine were co-administered. |
| Databáze: | OpenAIRE |
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