The ROCK inhibitor Fasudil prevents chronic restraint stress-induced depressive-like behaviors and dendritic spine loss in rat hippocampus
| Autor: | Gonzalo García-Rojo, Cristóbal Fresno, Nicolas A. Parra-Fiedler, Esteban Aliaga, Sergio Mora, Macarena Tejos, Jenny L. Fiedler, Paulina S. Rojas, Natalia Vilches, Claudio S. Parra, Gabriela Díaz-Véliz, Felipe I. Aguayo, Aníbal Pacheco |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Dendritic spine Hippocampus Antidepressant Hippocampal formation Rats Sprague-Dawley stress 0302 clinical medicine 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Protein Phosphatase 1 Pharmacology (medical) Chronic stress Phosphorylation Rho-associated protein kinase Neuronal Plasticity Depression Pyramidal Cells Fasudil Lim Kinases Psychiatry and Mental health Actin Depolymerizing Factors Restraint Physical medicine.medical_specialty Stress Behavior Dendritic spines 03 medical and health sciences Internal medicine medicine Animals ROCK inhibitor Fasudil Regular Research Article Protein Kinase Inhibitors Swimming Pharmacology antidepressant business.industry behavior Body Weight Immobility Response Tonic dendritic spines Dendrites Rats Disease Models Animal 030104 developmental biology Endocrinology Rho kinase inhibitor business Neuroscience 030217 neurology & neurosurgery Behavioural despair test |
| Zdroj: | International Journal of Neuropsychopharmacology |
| Popis: | Indexación: Web of Science; Scopus. Background: Dendritic arbor simplification and dendritic spine loss in the hippocampus, a limbic structure implicated in mood disorders, are assumed to contribute to symptoms of depression. These morphological changes imply modifications in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase. We have reported that chronic stress promotes depressive-like behaviors in rats along with dendritic spine loss in apical dendrites of hippocampal pyramidal neurons, changes associated with Rho kinase activation. The present study proposes that the Rho kinase inhibitor Fasudil may prevent the stress-induced behavior and dendritic spine loss. Methods: Adult male Sprague-Dawley rats were injected with saline or Fasudil (i.p., 10 mg/kg) starting 4 days prior to and maintained during the restraint stress procedure (2.5 h/d for 14 days). Nonstressed control animals were injected with saline or Fasudil for 18 days. At 24 hours after treatment, forced swimming test, Golgi-staining, and immuno-western blot were performed. Results: Fasudil prevented stress-induced immobility observed in the forced swimming test. On the other hand, Fasudiltreated control animals showed behavioral patterns similar to those of saline-treated controls. Furthermore, we observed that stress induced an increase in the phosphorylation of MYPT1 in the hippocampus, an exclusive target of Rho kinase. This change was accompanied by dendritic spine loss of apical dendrites of pyramidal hippocampal neurons. Interestingly, increased pMYPT1 levels and spine loss were both prevented by Fasudil administration. Conclusion: Our findings suggest that Fasudil may prevent the development of abnormal behavior and spine loss induced by chronic stress by blocking Rho kinase activity. https://academic.oup.com/ijnp/article/20/4/336/2632175 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|