ArticleNeurobiology of disease2019
Rho-kinase inhibition has antidepressant-like efficacy and expedites dendritic spine pruning in adolescent mice.
Article in Neurobiology of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Neurodegenerative Disease Associated Pathways in the Brains of Triple Transgenic Alzheimer's Model Mice Are Reversed Following Two Weeks of Peripheral Administration of Fasudil.International journal of molecular sciences · 2023Pooled it
- The ROCK Inhibitor Fasudil and Sertraline Share Morphological and Molecular Effects in the Hippocampus of Chronically Stressed Rats: Exploring Common Antidepressant Pathways by Network Pharmacology.ACS pharmacology & translational science · 2025Article
- Social experience in adolescence shapes prefrontal cortex structure and function in adulthood.Molecular psychiatry · 2024Article
- Role of Rho-associated kinases and their inhibitor fasudil in neurodegenerative diseases.Frontiers in neuroscience · 2024Review
- Mitophagy in depression: Pathophysiology and treatment targets.Mitochondrion · 2021Review
- Persistent behavioral and neurobiological consequences of social isolation during adolescence.Seminars in cell & developmental biology · 2021Review
- Semaphorin3F Drives Dendritic Spine Pruning Through Rho-GTPase Signaling.Molecular neurobiology · 2021Article
- Antidepressant-relevant behavioral and synaptic molecular effects of long-term fasudil treatment in chronically stressed male rats.Neurobiology of stress · 2020Article
- Determination of KD025 (SLx-2119), a Selective ROCK2 Inhibitor, in Rat Plasma by High-Performance Liquid Chromatography-Tandem Mass Spectrometry and its Pharmacokinetic Application.Molecules (Basel, Switzerland) · 2020Article
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5 authors at 1 institution in 1 country.
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Abstract
Adolescence represents a critical period of neurodevelopment, defined by structural and synaptic pruning within the prefrontal cortex. While characteristic of typical development, this structural instability may open a window of vulnerability to developing neuropsychiatric disorders, including depression. Thus, therapeutic interventions that support or expedite neural remodeling in adolescence may be advantageous. Here, we inhibited the neuronally-expressed cytoskeletal regulatory factor Rho-kinase (ROCK), focusing primarily on the clinically-viable ROCK inhibitor fasudil. ROCK inhibition had rapid antidepressant-like effects in adolescent mice, and its efficacy was comparable to ketamine and fluoxetine. It also modified levels of the antidepressant-related signaling factors, tropomyosin/tyrosine receptor kinase B and Akt, as well as the postsynaptic marker PSD-95, in the ventromedial prefrontal cortex (vmPFC). Meanwhile, adolescent-typical dendritic spine pruning on excitatory pyramidal neurons in the vmPFC was expedited. Further, vmPFC-specific shRNA-mediated reduction of ROCK2, the dominant ROCK isoform in the brain, had antidepressant-like consequences. We cautiously suggest that ROCK inhibitors may have therapeutic potential for adolescent-onset depression.
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