Food restriction has been widely associated with beneficial effects on brain aging and age-related neurodegenerative diseases such as Alzheimer's disease (AD). This irreversible, progressive brain disorder is associated with the accumulation of amyloid-beta into senile plaques and consequent synaptic dysfunction, neuronal loss, and changes in the activity of neural networks. As it is now also accepted that AD is characterized by decades-long, clinically silent prodromal phase of the disease,

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... present study was conducted with an aim to examine the effects of preventive intermittent, every-other-day (EOD) feeding regimen in the brain of the 5XFAD mice, a commonly used transgenic model of Alzheimer's disease. Female 5xFAD transgenic (Tg) mice and their non-transgenic littermates were exposed to ad libitum (AL) or EOD feeding regimen, beginning at 2 months of age. The general effects of EOD on plaque formation and gliosis were analyzed first, followed by the quantitative immunohistochemical analysis of two calcium-binding proteins, parvalbumin (PV) and calbindin (CB), in the dorsal hippocampus. A separate analysis of CA1, CA3, and DG hippocampal subregions was performed. Immunohistochemical analysis revealed a substantial increase of inflammation in the brain of 5XFAD mice following the EOD regimen, reflected by the increase in expression of microglial and astrocytic markers. This increase was accompanied by an increase of proinflammatory cytokine TNF-α in Tg-EOD mice in comparison to Tg-AL animals and furthermore, by the increase of parvalbumin-immunoreactivity in all subregions of dorsal hippocampus analyzed. The number of PV-expressing neurons was, however, not changed. Calbindin increase was detected only in CA3 subregion of the hippocampus. The present study demonstrates that every-other-day feeding regimen worsens inflammation in 5xFAD mice and further affects hippocampal calcium-binding proteins. EOD-induced increase in PV- and CB-immunoreactivity points to specific alteration in network excitability contri [...]