Cognitive–Exercise Dual-Task Intervention Ameliorates Cognitive Decline in Natural Aging Rats via Regulating lncRNA NEAT1/miR-124-3p/caveolin-1-PI3K/Akt/GSK3β Pathway

Abstract

Background: Aging induces degenerative changes in the body and causes cognitive dysfunction, which has a significant negative impact on the daily lives of older adults. At present, there are limited effective interventions to slow the incidence of Aging-related cognitive impairment or even dementia. Among them, exercise and cognitive training are worthy of further research, especially the research on mechanisms. Studies have shown that LncRNA and miRNA play an important role in the occurrence, development, and rehabilitation of aging-related cognitive impairment. We aimed to identify the effect of cognitive-exercise dual-task training on cognitive function in naturally aged rats and to investigate the mechanism by which the LncRNA NEAT1/miR124-3p/caveolin-1-PI3K/Akt/GSK3β pathway plays a role in the improvement of cognitive function with dual-task training. Methods: Forty SD rats at 18 months of age were randomly divided into four groups (n=10 for each group): exercise training group, cognitive training group, cognitive-exercise dual-task training group, and aging control group. Each group underwent 12 weeks of intervention according to their corresponding training protocols. New object recognition tests were performed on all rats after the completion of the intervention. The expressions of related pathway proteins, LncRNA, and miRNA in the hippocampus were examined by Western blotting (WB) and/or Quantitative real-time polymerase chain reactions (qRT-PCR) after euthanasia of the rats. HT22 mouse hippocampal neuronal cells were cultured and miR-124-3p and lncRNA NEAT1 were over-expressed/down-expressed, respectively. WB and/or qRT-PCR were used to determine the levels of caveolin-1-PI3K/Akt/GSK3 pathway, miR-124-3p, and lncRNA NEAT1 expression in the neurons. Results: The results showed that compared with the aging control group, the cognitive-exercise dual-task training group had better performance on novelty recognition (P < 0.01), and their expressions of lncRNA NEAT1, caveolin-1, and p-GSK3β were significantly decreased (P < 0.05), while miR124-3p, p-PI3K, and p-Akt were significantly increased (P < 0.05). Conclusion: Our study showed that cognitive-exercise dual-task training improved cognitive function in aging rats better than no training or single training. The mechanism of cognitive function improvement could be related to the regulation of LncRNA NEAT1/miR124-3p- caveolin1/PI3K/Akt/GSK3β pathway.

Cognitive‐exercise dual‐task promotes cognitive function recovery in chronic cerebral ischemia male rats through regulating PI3K/Akt signaling pathway via inhibition of EphrinA3/EphA4

“…Exercise training might attenuate hypoxia‐induced apoptosis and axonal growth capacity impairment through the release of miR‐126‐rich circulating endothelial progenitor cell‐derived exosomes (Wang et al., 2020). Moreover, exercise training further protects against MCAO‐induced neurological dysfunction by attenuating apoptotic cell death through activation of the PI3K/Akt/FoxO1 signaling pathway (Li, Tao, et al., 2023). Wang et al.…”

“…For example, Wang et al demonstrated that activation of Akt was engaged in the protection of exercise training against neuronal damage induced by CCI.Exercise training might attenuate hypoxia-induced apoptosis and axonal growth capacity impairment through the release of miR-126-rich circulating endothelial progenitor cell-derived exosomes(Wang et al, 2020). Moreover, exercise training further protects against MCAO-induced neurological dysfunction by attenuating apoptotic cell death through activation of the PI3K/Akt/FoxO1 signaling pathway(Li, Tao, et al, 2023). Wang et al also provide evidence that the role of exercise training in neurological injury is related to PI3K/Akt-GLT-1-Glutamat activation after CCI(Wang et al, 2014).…”

A hypothesis: MiRNA‐124 mediated regulation of sirtuin 1 and vitamin D receptor gene expression accelerates aging

“…The deterioration is often an outcome of genetic and epigenetic interference. This is an in silico search-derived hypothesis, on which further evidence can be proved, and based on the protocol an intervention model can be programmed in the future.Early detection of specific miRNAs and modulation of their expression by therapeutic intervention or using antisense oligonucleotide targeting miRNAs3,17,51 can be an analeptic target to decrease the probability of age-associated diseases. Altogether, this hypothesis provides a notion that circulating miRNAs as one of the epigenetic gene expression modulators and impede it can be an effective restorative target in the successful aging process.AUTH O R CO NTR I B UTI O N SMs.…”