Neuropeptide Y as A Key Mediator in Environmental Enrichment-Induced Cognitive Protection in Alzheimer's Disease

Abstract

Neuropeptide Y (NPY) is a prominent neuromodulator in the brain, playing a critical role in regulating stress responses, mood, and neuroplasticity. It influences various behavioural processes, including appetite, reward, and anxiety. Environmental enrichment (EE), which involves exposure to a stimulating environment with physical, social, and cognitive components, has been shown to promote brain health by enhancing neuroplasticity, neurogenesis, and cognitive function. This review examines the potential link between NPY and Alzheimer's disease (AD), suggesting that NPY may modulate the positive effects of EE on brain function in the context of neurodegeneration. Existing evidence indicates that EE can alter NPY expression, which in turn might influence neuroplasticity, neuronal survival, and resilience to neurodegeneration. In animal studies, EE has been shown to increase NPY levels, which are associated with improved cognitive performance, reduced anxiety, and enhanced neurogenesis, particularly in the hippocampus—the region most affected by Alzheimer's disease. Furthermore, NPY’s interactions with other neurotrophic factors, such as BDNF and IGF-1, further support its involvement in counteracting the neurological deficits seen in AD. The potential therapeutic implications of targeting NPY for AD, including its role in cognitive decline and neuroprotection, are promising. However, challenges remain, including inconsistent experimental approaches and a lack of long-term human clinical trials. Future research should focus on elucidating the molecular mechanisms by which NPY influences EE-induced effects, with the aim of developing innovative, non-pharmacological interventions for Alzheimer's disease and related neurodegenerative disorders