Knockdown of lncRNA TUG1 inhibits hippocampal neuronal apoptosis and participates in aerobic exercise-alleviated vascula
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(2020) 53:53 Wang et al. Biol Res https://doi.org/10.1186/s40659-020-00320-4
Open Access
RESEARCH ARTICLE
Knockdown of lncRNA TUG1 inhibits hippocampal neuronal apoptosis and participates in aerobic exercise‑alleviated vascular cognitive impairment Jing Wang1†, Yali Niu1†, Huaying Tao2, Mina Xue3 and Chunxiao Wan1*
Abstract Objectives: Our previous study indicated that aerobic exercise relieves cognitive impairment in patients with vascular cognitive impairment (VCI) via regulating brain-derived neurotrophic factor (BDNF), but the mechanism is not yet clear. This study aimed to explore whether lncRNA taurine upregulated gene 1 (TUG1) participates in the process of VCI by regulating BDNF. Methods: The expressions of TUG1 and BDNF in the serum of VCI patients were detected. The potential molecular mechanisms of TUG1 in regulating hippocampal neuronal apoptosis were explored in oxygen and glucose deprivation-induced (OGD-induced) hippocampal cell line HT22. The VCI mouse model was established, and TUG1 and BDNF were overexpressed via lentivirus injection. The cognitive impairment of mice was detected by the Morris water maze experiment after the aerobic exercise. Results: The level of TUG1 was elevated in the serum of VCI patients compared with the control group. The knockdown of TUG1 in OGD-induced HT22 cells increased BDNF level and decreased cell apoptosis, and the downregulation of BDNF restored the decreased cell apoptosis. RNA immunoprecipitation and RNA pull-down assays showed that TUG1 could bind to BDNF protein. The aerobic exercise alleviated cognitive impairment and inhibited hippocampal apoptosis in VCI mice. Meanwhile, the overexpression of TUG1 reversed the therapeutic effects of aerobic exercise on cognitive impairment. Conclusions: The knockdown of TUG1 reduced hippocampal neuronal apoptosis and participates in the aerobic exercise-alleviated VCI, which was partly through regulating BDNF. Keywords: Vascular cognitive impairment, lncRNA TUG1, BDNF, Aerobic exercise
*Correspondence: [email protected] † Jing Wang and Yali Niu contributed equally to this work and should be regarded as co-first authors 1 Department of Physical and Rehabilitation Medicine, Tianjin Medical University General Hospital, No. 154 Anshan Road, Peace District, Tianjin 300070, People’s Republic of China Full list of author information is available at the end of the article
Introduction Vascular cognitive impairment (VCI) is a cognitive impairment caused by vascular diseases, including mild cognitive impairment and dementia [1]. So far, the pathogenesis of VCI is not clear, and there is no effective treatment, which can only be prevented via treating vascular diseases and other VCI risk factors [1, 2]. Studies have revealed that aerobic exercise improves cardiovascular function in adults and also improves cognitive performance in patients with VCI [3–5]. Nevertheless,
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