N-Pep-12 Improves Hippocampal Cognitive Function and Increases Neuroplasticity and Neurogenesis Markers

This study investigates the effects of N‑PEP‑12, a neuroprotective dietary supplement, on cognitive function, neuroplasticity, and neurogenesis in aged 129S1/SvImJ (S1) mice, which are known for age‑associated cognitive impairments. The primary objective was to determine whether N‑PEP‑12 could improve memory retention and enhance neural health by modulating hippocampal plasticity and neurogenesis. S1 mice were chronically treated with N‑PEP‑12 or a Vehicle to assess its impact on cognitive performance using cued fear conditioning (CFC) and object location memory (OLM) tests. Additionally, in vitro studies examined the effects of N‑PEP‑12 on neuroplasticity markers such as Neurofilament Light Chain (NF‑L) expression and vasopressin (AVP) promoter methylation, to elucidate the molecular mechanisms underlying cognitive enhancements. N‑PEP‑12 treatment significantly improved associative and contextual memory in the CFC and OLM tests respectively. In vitro assays revealed that N‑PEP‑12 increased NF‑L expression and decreased AVP promoter methylation, indicating enhanced neuroplasticity and neurogenesis. Furthermore, N‑PEP‑12 preserved blood‑brain barrier integrity under oxidative stress conditions, suggesting a protective role against vascular‑related cognitive decline. The findings suggest that N‑PEP‑12 promotes hippocampal health by enhancing neurogenesis and neuroplasticity, potentially mitigating age‑related cognitive decline. These results highlight N‑PEP‑12 as a promising agent for supporting healthy cognitive function in aging populations through the modulation of neurobiological pathways associated with learning and memory.