Dendritic spine degeneration is associated with age-related decline in recognition and spatial memory in male mice

Human populations are experiencing an increase in aging, which is associated with cognitive deficits. Animal models of aging have shown that these behavioral impairments are associated with neuroarchitecture modifications in the prefrontal cortex (PFC) and hippocampus; however, most studies have focused on rats or lack multiple key ages. In this study, we evaluated spatial and recognition memory in male mice at critical ages [3 months (M), 6, 12 and 18] using the Morris water maze (MWM) and novel object recognition test (NORT), respectively. Moreover, we quantified dendritic arborization, spine density and the type of spines in the PFC, CA1 hippocampus and nucleus Accumbens Core (NAcC). Locomotion, assessed in the first phase of NORT, revealed age-dependent reductions. Notably, the 18 M group revealed significant recognition memory deficits. Spatial memory impairments were especially evident at the 12 M group in the MWM. Spine density was increased at 6 M in the NAcC, whereas a reduction was noted at 12 M and 18 M in the PFC. Morphological assessment of spines indicated age-dependent changes, including a notable increase in the proportion of thin spines in the CA1 and PFC regions. However, dendritic arborization remained largely unchanged across the examined brain regions and age groups. Overall, our findings observed age-dependent alterations in memory and morphological alterations in spines in mice, emerging as possible contributors to cognitive decline. These results highlight the potential for anti-aging interventions targeting synaptic structures to enhance cognitive health and extend the healthspan of aging individuals.