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28 July 2019 : Animal Research  

Cerebellar Fastigial Nucleus Stimulation in a Chronic Unpredictable Mild Stress Rat Model Reduces Post-Stroke Depression by Suppressing Brain Inflammation via the microRNA-29c/TNFRSF1A Signaling Pathway

Mu Wang1ABCE, Jian Guo2ABDE, Li-na Dong3CEF, Jun-Ping Wang4BEG*

DOI: 10.12659/MSM.911835

Med Sci Monit 2019; 25:5594-5605


BACKGROUND: We previously reported that cerebellar fastigial nucleus stimulation reduced post-stroke depression in a rat model by reducing inflammation. This study aimed to investigate the molecular inflammatory signaling pathways associated with cerebellar fastigial nucleus stimulation in an established rat model of post-stroke depression.

MATERIAL AND METHODS: Twenty-four Sprague-Dawley rats included a sham group (N=6), an untreated stroke group (N=6), an untreated post-stroke depression model group (PSD) (N=6), and the model group treated with cerebellar fastigial nucleus stimulation (FNS) (N=6). The rat stroke model involved occlusion of the middle cerebral artery occlusion (MCAO). Post-stroke depression model was established using chronic unpredictable mild stress treatment and was verified using an open field test. Real-time polymerase chain reaction (PCR) and Western blot compared expression levels of microRNA-29c (miR-29c), miR-676, TNFRSF1A, tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β in cerebellar tissue. U251 human glioblastoma cells and SH-SY5Y human neuroblastoma cells were studied in vitro.

RESULTS: Cerebellar fastigial nucleus stimulation reduced behaviors associated with depression in the rat model, upregulated the expression of miR-29c, and reduced the expression of TNFRSF1A and inflammatory cytokines, and mildly reduced neuronal apoptosis. Bioinformatics data analysis identified a regulatory relationship between miR-29c and TNFRSF1A. SH-SY5Y cells treated with a miR-29c mimic, or TNFRSF1A short interfering RNA (siRNA), identified a negative regulatory relationship between TNFRSF1A and miR-29c.

CONCLUSIONS: In a rat model, cerebellar fastigial nucleus stimulation reduced the expression of TNFRSF1A by upregulating miR-29c expression, which suppressed the expression of inflammatory cytokines, resulting in reduced severity of post-stroke depression.

Keywords: Depression, Brain Ischemia, Cell Line, Cerebellar Nuclei, Deep Brain Stimulation, Depressive Disorder, Encephalitis, Infarction, Middle Cerebral Artery, Receptors, Tumor Necrosis Factor, Type I, Stress, Physiological, Stroke

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01 November 2023 : Editorial  

Editorial: Factors Driving New Variants of SARS-CoV-2, Immune Escape, and Resistance to Antiviral Treatments as the End of the COVID-19 Pandemic is Declared

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville,

DOI: 10.12659/MSM.942960

Med Sci Monit 2023; 29:e942960


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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750