An analysis of the therapeutic efficacy and underlying mechanisms of combining lycopene with dental pulp stem cells to ameliorate alzheimer's disease in rats.

The choroid plexus (CP), which is responsible for forming the blood-cerebrospinal fluid barrier, contributes to the modulation of deficits in Alzheimer’s disease (AD) by enhancing neuroinflammatory and brain immune responses. Previous research has demonstrated that lycopene (LYCO) or dental pulp stem cells (DPSCs) can attenuate AD-related inflammatory responses. However, it remains unclear whether LYCO and DPSCs can synergistically ameliorate neuroinflammation in the CP. Therefore, this study aims to investigate the feasibility of combining LYCO with DPSCs to mediate immunomodulatory effects within the CP in a rat model of AD. The findings indicated that oral administration of LYCO, transplantation of DPSCs, and the combination of these two methods significantly enhanced the learning and memory capabilities of AD rats in the water maze test, including improvements in directional sense and spatial orientation abilities. Furthermore, these treatments were associated with a reduction in pro-inflammatory mediators (TNF-α and IL-1β) and an increase in anti-inflammatory mediators (IL-10 and TGF-β1) within cerebrospinal fluid and hippocampal tissue. Furthermore, treatment with LYCO, DPSCs, or their combination effectively reverses Aβ1−42-induced upregulation of Toll-like receptor 4 expression at both mRNA and protein levels, as well as the expression of NF-κB p65. This study presents novel experimental evidence supporting the combined therapeutic potential of LYCO and DPSCs in modulating immune responses within the CP, while also offering valuable insights into the pathophysiology of AD and potential mechanisms associated with CP.