Cognitive improvement following ischemia/reperfusion injury induced by voluntary running‑wheel exercise is associated with LncMALAT1‑mediated apoptosis inhibition.

Abstract

Previous human and animal studies demonstrated that voluntary exercise may improve cognitive function and facilitate neuronal plasticity in ischemia/reperfusion (I/R) models. However, the possible underlying mechanisms remain to be elucidated. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long noncoding RNA (lncRNA), may be associated with the functions and dysfunctions of endothelial cells. The present study investigated whether spontaneous running-wheel (RW) exercise-induced MALAT1 expression changes may be associated with the cognitive improvement of mice following I/R injury. The expression of MALAT1 was evaluated using reverse transcription-quantitative polymerase chain reaction. Artificial MALAT1 and MALAT1 lentiviral mall interfering (siRNA) were used to alter MALAT1 expression levels in vivo. The Morris Water Maze test was performed to evaluate spatial learning and memory retention in the mice. Changes in the apoptotic rates of hippocampal neurons and levels of apoptosis-associated proteins were also detected. The data revealed that MALAT1 increased in the hippocampus of mice in the RW-treated I/R group and that this was associated with neurological, learning and memory improvement, reduced infarction volumes, decreased apoptosis and alterations to expression levels of apoptosis-associated proteins. Following RW training in I/R-injured mice, lentiviral MALAT1 siRNA conduction partially attenuated the protections induced by voluntary RW. However, exogenous MALAT1 treatment increased the protection. The current findings suggested that voluntary RW protected hippocampal neurons from I/R injury and promoted cognitive restoration, which was associated with lncRNA MALAT1-mediated apoptosis inhibition.