Antidepressant-relevant behavioral and synaptic molecular effects of long-term fasudil treatment in chronically stressed male rats

Román-Albasini, Luciano; Dı́az-Véliz, Gabriela; Olave, Felipe Antonio; Aguayo, Felipe I.; García-Rojo, Gonzalo; Corrales, Wladimir A.; Silva, Juan Pablo; Avalos, Ana M.; Rojas, Paulina S.; Aliaga, Esteban; Fiedler, Jenny L.

doi:10.1016/j.ynstr.2020.100234

Cited by 14 publications

(12 citation statements)

References 76 publications

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“…Recent studies have demonstrated that the depression associated with chronic stress was accompanied with dendritic remodeling in hippocampal neurons (37,38). Notably, the brain-derived microRNAs could regulate dendritic spine development and may thus be involved in regulating neural plasticity and behaviors (39,40). In order to further explore functions of the miR-26a-3p/PTEN axes as related to depression, we utilized the CUMSinduced rat model of depression.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies

Li¹,

Fan²,

Wang³

et al. 2021

Journal of Clinical Investigation

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Depression is a neuropsychiatric disease associated with neuronal anomalies within specific brain regions. In the present study, we screened microRNA (miRNA) expression profiles in the dentate gyrus (DG) of hippocampus and found miR-26a-3p was markedly down-regulated in the rat model of depression, whereas up-regulation of miR-26a-3p within DG regions rescued the neuronal deterioration and depression-like phenotypes resulting from stress exposure, effects which appear to be mediated by the PTEN pathway.The knock-down of miR-26a-3p in DG regions of normal control rats induced depressionlike behaviors, effects which were accompanied with an activation of PTEN-PI3K/Akt signaling pathway and neuronal deterioration via suppression of autophagy, impairments in synaptic plasticity and the promotion of neuronal apoptosis. In conclusion, these results suggested that a miR-26a-3p deficits within the hippocampal DG mediated the neuronal anomalies contributing to the display of depression-like behaviors. This miRNA may serve as a potential therapeutic target for the treatment of depression.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies

Li¹,

Fan²,

Wang³

et al. 2021

Journal of Clinical Investigation

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“…In GluA1-deficient mice, hippocampal LTP was absent without spatial reference memory deficits [67], but working memory deficits [68], schizophrenia-like behaviors [69,70] and increased locomotor activity, accompanied by reduced clearance of striatal dopamine, was displayed [69]. While GWAS identified GluA1 dysfunction as a risk factor for schizophrenia [12], molecular and pharmacological studies over the past decade have linked GluA1 to depression, anxiety, stress-related behavior, and Alzheimer's disease [71][72][73][74]. Interestingly, the levels of GluA1 expression and phosphorylation appear to be important for these neurological conditions [71,73,75,76].…”

Section: Figurementioning

confidence: 99%

“…While GWAS identified GluA1 dysfunction as a risk factor for schizophrenia [12], molecular and pharmacological studies over the past decade have linked GluA1 to depression, anxiety, stress-related behavior, and Alzheimer's disease [71][72][73][74]. Interestingly, the levels of GluA1 expression and phosphorylation appear to be important for these neurological conditions [71,73,75,76]. In the future, it would be interesting to determine whether the phosphorylation state of GluA1 is modified by its interaction with Np65 or by the loss of neuroplastin.…”

Section: Figurementioning

confidence: 99%

Neuroplastin in Neuropsychiatric Diseases

Lin

Liang

Herrera-Molina

et al. 2021

Genes

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Molecular mechanisms underlying neuropsychiatric and neurodegenerative diseases are insufficiently elucidated. A detailed understanding of these mechanisms may help to further improve medical intervention. Recently, intellectual abilities, creativity, and amnesia have been associated with neuroplastin, a cell recognition glycoprotein of the immunoglobulin superfamily that participates in synapse formation and function and calcium signaling. Data from animal models suggest a role for neuroplastin in pathways affected in neuropsychiatric and neurodegenerative diseases. Neuroplastin loss or disruption of molecular pathways related to neuronal processes has been linked to various neurological diseases, including dementia, schizophrenia, and Alzheimer’s disease. Here, we review the molecular features of the cell recognition molecule neuroplastin, and its binding partners, which are related to neurological processes and involved in learning and memory. The emerging functions of neuroplastin may have implications for the treatment of diseases, particularly those of the nervous system.

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“…The Fasudil, a potent ROCK inhibitor has been approved for clinical use in Japan for the treatment of subarachnoid hemorrhage, and cerebral vasospasm. It was also shown to increase motor neuron survival, and inhibit axonal degeneration, enhances axonal regeneration, and modulates microglial function in vitro and in vivo (Bandarage et al, 2021;De et al, 2019;Koch et al, 2020;Mietzner et al, 2020;Román-Albasini et al, 2020;Tatenhorst et al, 2016;Wang et al, 2020;Zhao et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Design and development of novel fasudil derivatives as potent antibreast cancer agent that improves intestinal flora and intestinal barrier function in rats

et al. 2021

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This study was conducted to develop novel fasudil derivatives after incorporation of substituted thiazoles as potent anti-breast cancer (BC) agents. The compounds were developed using a facile synthetic route in excellent yields. The entire set of developed compounds was tested for inhibitory activity against rho-associated coiled-coil kinase (ROCK; ROCK1 and ROCK2) kinase, where they exhibit potent and selective inhibition of ROCK1 as compared to ROCK2. The most potent ROCK2 inhibitor, compound 6h significantly inhibited the viability of BC cells (MCF-7). It also causes inhibition of migration and invasion of MCF-7 cells.Moreover, the anti-BC activity of compound 6h was studied in 7,12 dimethyl Benz(a)anthracene (DMBA)-induced BC in female Sprague Dawley rats. Results suggest that it causes significant improvement in the bodyweight of the animals with a reduction in oxidative stress in the liver and mammary tissues of rats. It showed improvement in the intestinal barrier function of rats by restoring the level of Diamine oxidase, d-lactate, and endotoxin. In western blot analysis, it showed improvement in (ZO-1), occludin, and claudin-1 in the colon tissue of the rat as compared to the DMBA group. Our study demonstrated the development of the novel class of fasudil derivatives potent anti-BC agent that improves intestinal flora and intestinal barrier function in rats.

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Antidepressant-relevant behavioral and synaptic molecular effects of long-term fasudil treatment in chronically stressed male rats

Cited by 14 publications

References 76 publications

MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies

MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies

Neuroplastin in Neuropsychiatric Diseases

Design and development of novel fasudil derivatives as potent antibreast cancer agent that improves intestinal flora and intestinal barrier function in rats

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