Masticatory Function and Cognitive Health: Investigating a Molecular Connection Between Oral Tissues and the Brain

Abstract

Background: Amongst the rapidly growing elderly population, there is increasing need for comprehensive prosthodontic treatment to address impaired masticatory function of many etiologies3. Compromised oral health may contribute to a myriad of systemic pathologies, including cognitive decline. Several studies have observed an association between poor masticatory function in elderly patients and impaired cognitive function6. Previously, we identified a novel retrograde transport mechanism of exosomal neprilysin, a neuroprotective enzyme, from the masseter muscle to the hippocampus through the trigeminal nerve4. Aim: This study aims to identify additional neurotrophic agents that are produced in various oral tissues (OT) and retrogradely transported to the brain. Project-design: This study evaluates: 1) neurotrophic mRNA expression profiles in murine cells from submandibular-glands (SMG), dental-pulp (DP), brain-astrocytes (AST), and neuronal cell line (CATHa) using next-generation-sequencing; 2) protein expression of brain-derived growth factor (BDNF) and nerve growth factor (NGF) in SMG/DP cells versus AST/CATHa-cells via Western blot; and 3) the growth support of CATHa by exosomes isolated from other cells. Preliminary-results:

Neurotrophic mRNAs were significantly overexpressed in SMG/DP cells versuss AST/CATHa. Western blot analysis of BDNF/NGF protein expression in SMG/DP cells was abundant, but minimal in AST/CATHa. Conclusion: OT-cells exhibit higher neurotrophic mRNA expression than brain-cells, with corresponding proteins abundant in OT-derived exosomes. This suggests that OTs may play a crucial role in supplying essential biomolecules to the brain. Results from this ongoing study further highlight the impact of masticatory function and oral health on systemic health and provides hope for development of therapeutics.