Antidepressant-like effect of guanosine involves activation of AMPA receptor and BDNF/TrkB signaling
| Autor: | Yasmim de Oliveira Dalsenter, Morgana Moretti, Mauren K. Tavares, Priscila B. Rosa, Ana Lúcia S. Rodrigues, Daiane B. Fraga, Isabella A. Heinrich, Fernanda Neutzling Kaufmann, Luis E.B. Bettio, Vivian B. Neis, Andiara E. Freitas, Rodrigo B. Leal, Nicolle Platt, Isabel Werle, Axel Fogaça Rosado |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Synapsin I Dendritic spine Dendritic Spines Neurogenesis Prefrontal Cortex Guanosine Tropomyosin receptor kinase B AMPA receptor Hippocampal formation Hippocampus Mice 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine DNQX Animals Receptors AMPA Molecular Biology Membrane Glycoproteins Chemistry Brain-Derived Neurotrophic Factor Dentate gyrus Feeding Behavior Cell Biology Protein-Tyrosine Kinases Antidepressive Agents 030104 developmental biology Endocrinology Hindlimb Suspension nervous system Synapses Original Article Female Calcium Channels 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Purinergic Signal |
| ISSN: | 1573-9546 1573-9538 |
| Popis: | Guanosine is a purine nucleoside that has been shown to exhibit antidepressant effects, but the mechanisms underlying its effect are not well established. We investigated if the antidepressant-like effect induced by guanosine in the tail suspension test (TST) in mice involves the modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, voltage-dependent calcium channel (VDCC), and brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) pathway. We also evaluated if the antidepressant-like effect of guanosine is accompanied by an acute increase in hippocampal and prefrontocortical BDNF levels. Additionally, we investigated if the ability of guanosine to elicit a fast behavioral response in the novelty suppressed feeding (NSF) test is associated with morphological changes related to hippocampal synaptogenesis. The antidepressant-like effect of guanosine (0.05 mg/kg, p.o.) in the TST was prevented by DNQX (AMPA receptor antagonist), verapamil (VDCC blocker), K-252a (TrkBantagonist), or BDNF antibody. Increased P70S6K phosphorylation and higher synapsin I immunocontent in the hippocampus, but not in the prefrontal cortex, were observed 1 h after guanosine administration. Guanosine exerted an antidepressant-like effect 1, 6, and 24 h after its administration, an effect accompanied by increased hippocampal BDNF level. In the prefrontal cortex, BDNF level was increased only 1 h after guanosine treatment. Finally, guanosine was effective in the NSF test (after 1 h) but caused no alterations in dendritic spine density and remodeling in the ventral dentate gyrus (DG). Altogether, the results indicate that guanosine modulates targets known to be implicated in fast antidepressant behavioral responses (AMPA receptor, VDCC, and TrkB/BDNF pathway). [Image: see text] |
| Databáze: | OpenAIRE |
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