Ca2+-Permeable TRPV1 Receptor Mediates Neuroprotective Effects in a Mouse Model of Alzheimer's Disease via BDNF/CREB Signaling Pathway.

Abstract

Transient receptor potential vanilloid 1 (TRPV1) protein is a Ca2+-permeable non-selective cation channel known for its pain modulation pathway. In a previous study, it was discovered that a triple-transgenic Alzheimer's disease (AD) mouse model (3xTg-AD+/+) has anti-AD effects. The expression of proteins in the brain-derived neurotrophic factor (BDNF)/cAMP response element binding protein (CREB) pathway in a 3xTg-AD/TRPV1 transgenic mice model was investigated to better understand the AD regulatory effect of TRPV1 deficiency. The results show that TRPV1 deficiency leads to CREB activation by increasing BDNF levels and promoting phosphorylation of tyrosine receptor kinase B (TrkB), extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and CREB in the hippocampus. Additionally, TRPV1 deficiency-induced CREB activation increases the antiapoptotic factor B-cell lymphoma 2 (Bcl-2) gene, which consequently downregulates Bcl-2-associated X (Bax) expression and decreases cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP), which leads to the prevention of hippocampal apoptosis. In conclusion, TRPV1 deficiency exhibits neuroprotective effects by preventing apoptosis through the BDNF/CREB signal transduction pathway in the hippocampus of 3xTg-AD mice.