Cell-type-specific expression of Nav1.6 in the developing brain of mice and its involvement in glial activation in Alzheimer's disease

Abstract

Voltage-gated sodium channels (Nav's), particularly Nav1.6, are crucial for action potential generation in neurons and are linked to brain disorders. This study explores the cell-type-specific expression of Nav1.6 in C57BL/6 mice brains at various developmental stages. Coronal sections from embryonic day 14 to postnatal day 30 were examined. Nav1.6 expression increased at both protein and messenger RNA (mRNA) levels during this period. Immunofluorescence double staining revealed that Nav1.6 is primarily localized on neurons. Astrocytes show increasing expression from prenatal to postnatal stages, correlating with maturation. Microglia exhibit low-intensity expression throughout the development. Co-expression of Nav1.6 with oligodendrocyte precursor cell marker NG2 is observed from E14 through postnatal stages, with prominent co-expression on day 21 and day 30. Consistent co-expression with olig2 is observed from E16 to day 30. In primary cultures, astrocytes had higher Nav1.6 levels compared to microglia and oligodendrocyte precursor cells. Nav1.6 expression was upregulated in astrocytes and microglia in APP/amyloid beta precursor protein/presenilin 1 (PS1) transgenic mice. Down-regulating Nav1.6 in vitro reduced amyloid beta-induced microglial activation and cytokine levels (IL-1β, TNF-α). These findings highlight Nav1.6 as a potential target for therapeutic interventions against neurodegenerative diseases.

Keywords: astrocyte; microglia; neuron; oligodendrocyte precursor cells; voltage-gated sodium channels Nav1.6.