Please use this identifier to cite or link to this item: https://doi.org/10.3390/cells10092476
Title: Early life irradiation-induced hypoplasia and impairment of neurogenesis in the dentate gyrus and adult depression are mediated by microrna-34a-5p/t-cell intracytoplasmic antigen-1 pathway
Authors: Wang, H 
Ma, Z
Shen, H
Wu, Z
Liu, L
Ren, B
Wong P.S. 
Sethi, G 
Tang, F 
Keywords: depression
miR-34a-5p
neurogenesis
tia1
γ-irradiation
Animals
Apoptosis
Cell Proliferation
Dentate Gyrus
Depression
Gamma Rays
Gene Expression Regulation, Neoplastic
Mice
Mice, Inbred BALB C
MicroRNAs
Neurogenesis
T-Cell Intracellular Antigen-1
Issue Date: 1-Sep-2021
Publisher: MDPI AG
Citation: Wang, H, Ma, Z, Shen, H, Wu, Z, Liu, L, Ren, B, Wong P.S., Sethi, G, Tang, F (2021-09-01). Early life irradiation-induced hypoplasia and impairment of neurogenesis in the dentate gyrus and adult depression are mediated by microrna-34a-5p/t-cell intracytoplasmic antigen-1 pathway. Cells 10 (9) : 2476-2476. ScholarBank@NUS Repository. https://doi.org/10.3390/cells10092476
Abstract: Early life radiation exposure causes abnormal brain development, leading to adult de-pression. However, few studies have been conducted to explore pre-or post-natal irradiation-in-duced depression-related neuropathological changes. Relevant molecular mechanisms are also poorly understood. We induced adult depression by irradiation of mice at postnatal day 3 (P3) to reveal hippocampal neuropathological changes and investigate their molecular mechanism, focus-ing on MicroRNA (miR) and its target mRNA and protein. P3 mice were irradiated by γ-rays with 5Gy, and euthanized at 1, 7 and 120 days after irradiation. A behavioral test was conducted before the animals were euthanized at 120 days after irradiation. The animal brains were used for different studies including immunohistochemistry, CAP-miRSeq, Real-Time Quantitative Reverse Transcrip-tion PCR (qRT-PCR) and western blotting. The interaction of miR-34a-5p and its target T-cell intra-cytoplasmic antigen-1 (Tia1) was confirmed by luciferase reporter assay. Overexpression of Tia1 in a neural stem cell (NSC) model was used to further validate findings from the mouse model. Irradiation with 5 Gy at P3 induced depression in adult mice. Animal hippocampal pathological changes included hypoplasia of the infrapyramidal blade of the stratum granulosum, aberrant and impaired cell division, and neurogenesis in the dentate gyrus. At the molecular level, upregulation of miR-34a-5p and downregulation of Tia1 mRNA were observed in both animal and neural stem cell models. The luciferase reporter assay and gene transfection studies further confirmed a direct interaction between miR-43a-5p and Tia1. Our results indicate that the early life γ-radiation-acti-vated miR-43a-5p/Tia1 pathway is involved in the pathogenesis of adult depression. This novel finding may provide a new therapeutic target by inhibiting the miR-43a-5p/Tia1 pathway to prevent radiation-induced pathogenesis of depression.
Source Title: Cells
URI: https://scholarbank.nus.edu.sg/handle/10635/210296
ISSN: 2073-4409
DOI: 10.3390/cells10092476
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