Integrated Aerobic Exercise and Multisensory Environment Training for Age-related Cognitive Decline via...

Area of Science:

• Neuroscience
• Aging Research
• Cognitive Science

Background:

• Age-associated cognitive decline presents a significant challenge to elderly health.
• Existing interventions like aerobic exercise and environmental enrichment show promise but lack clear mechanistic understanding.
• The neural underpinnings of cognitive improvement in aging remain largely unexplored.

Purpose of the Study:

• To investigate the efficacy of a novel combined training (CT) intervention comprising aerobic exercise (AE) and multisensory stimulation environment training (MSET) on cognitive decline in aged mice.
• To elucidate the neural mechanisms, particularly the role of the hippocampus-prefrontal cortex (HPC-PFC) circuit, underlying the cognitive benefits of CT.
• To identify molecular targets modulated by CT in the HPC and PFC.

Main Methods:

• Development and application of a combined training (CT) regimen in aged mice.
• Assessment of cognitive function following CT, AE, MSET, or control conditions.
• Neural circuit tracing and chemogenetics to probe the HPC-PFC circuit's role.
• Single-cell sequencing to identify molecular changes in the HPC and PFC.

Main Results:

• CT significantly mitigated cognitive decline in aged mice, outperforming individual AE or MSET.
• CT increased neuronal activity and synaptic plasticity in the hippocampus (HPC) and prefrontal cortex (PFC).
• HPC-PFC circuit manipulation demonstrated its critical role in CT-mediated cognitive enhancement.
• CT modulated specific molecular targets: PCSK1N and LY6H by AE, and DPP6 and GRINA by MSET, with CT upregulating these molecules.

Conclusions:

• Combined training (CT) offers a potent strategy for mitigating age-associated cognitive decline.
• The HPC-PFC neural circuit is crucial for the cognitive benefits observed with CT.
• CT-induced molecular changes in the HPC and PFC contribute to cognitive improvement, providing potential therapeutic targets.