Repeated VU0155069 Treatment Is Associated with Region- and Pathological Stage-Specific Dendritic Spine Remodeling in Female 3xTg-AD Mice

Repeated VU0155069 treatment in female 3xTg-AD mice is linked to region- and pathological stage-specific dendritic spine remodeling, with recurring changes in spine-subtype distribution and morphometry rather than uniform rescue.

• Why it matters: AD-related pathological states are associated with synaptic integrity loss, and prior work showed functional resilience plus CA1 spine integrity; this study tests how that resilience appears structurally across circuits and stages.
• What they did: Female 3xTg-AD mice received vehicle or VU0155069 (1 mg/kg intraperitoneally every other day) for one month starting at 5 or 11 months, with Golgi-Cox analysis at 6 or 12 months versus age-matched vehicle-treated littermates.
• The result: Auditory/visual cortex, hippocampal CA2, CA3, and DG, and central/lateral/basolateral amygdalar nuclei showed distinct, nucleus- and stage-dependent spine abundance, density, geometry, and subtype redistribution, implying circuit-specific structural engagement.