Low-Molecular Weight BDNF Mimetic, Dimeric Dipeptide GSB-106, Reverses Depressive Symptoms in Mouse Chronic Social Defeat Stress
| Autor: | I. O. Logvinov, Armen G. Mezhlumyan, Anna V. Tallerova, Polina Povarnina, Tatiana A Gudasheva, T. A. Antipova, Yulia N. Firsova, Sergey B. Seredenin |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Male lcsh:QR1-502 Administration Oral dipeptide mimetic Tropomyosin receptor kinase B Biochemistry Hippocampus lcsh:Microbiology Indole Alkaloids Social defeat Mice 0302 clinical medicine Biomimetic Materials Estrenes Mice Inbred BALB C Membrane Glycoproteins Neuronal Plasticity antidepressant-like activity biology Behavior Animal Chemistry Dipeptides Protein-Tyrosine Kinases Antidepressive Agents Pyrrolidinones chronic social defeat stress medicine.medical_specialty Carbazoles Synaptophysin Diamines CREB Article 03 medical and health sciences GSB-106 Internal medicine medicine Animals Social Behavior Molecular Biology PI3K/AKT/mTOR pathway Depressive Disorder Brain-Derived Neurotrophic Factor Antagonist Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology BDNF Trk receptor biology.protein Peptidomimetics 030217 neurology & neurosurgery Behavioural despair test |
| Zdroj: | Biomolecules Biomolecules, Vol 11, Iss 252, p 252 (2021) Volume 11 Issue 2 |
| ISSN: | 2218-273X |
| Popis: | A mimetic of the BDNF loop 4, bis (N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide, named GSB-106, was designed and synthesized in our scientific group. The compound activated TrkB, MAPK/ERK, PI3K/AKT, and PLCγ in in vitro experiments. In vivo experiments with rodents revealed its antidepressant-like activity in the forced swim and the tail suspension tests at the dose range of 0.1–5.0 mg/kg (i.p., p.o.). However, GSB-106 was not studied in depression models modulating major depression in humans. In the present study, the GSB-106 antidepressant-like activity was revealed in mice at the depression model induced by 28-day social defeat stress with 21-days oral administration (0.1 mg/kg) after stress. At the same time, GSB-106 restored reduced locomotor activity and completely eliminated the anhedonia manifestations. The compound also restored reduced levels of synaptophysin and CREB in the hippocampus. In addition, the Trk receptor antagonist K252A, and the PLC inhibitor U73122, were found to completely block the antidepressant-like activity of GSB-106 in the forced swimming test in mice. Thus, the present results demonstrate the dipeptide BDNF mimetic GSB-106 reversed depressive-like behavior and restored hippocampal neuroplasticity in a rodent depression model. These effects of GSB-106 are probably regulated by TrkB signaling. |
| Databáze: | OpenAIRE |
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