Exploring the impact of food restriction on cognitive and psychological behaviors in young mice: insights on biochemical, molecular, and histologic analysis of the hippocampus

Nutrition is crucial for mental well-being and enhancing cognitive performance. Food restriction (FR), a moderate reduction in food intake, results in multiple effects on brain function. Most studies of FR have been conducted on adult animals rather than young ones. This study examines the acute effect of early-onset FR, starting at four-week age, on behavioral performance, molecular changes, and histological changes. Young mice were randomly assigned to four experimental groups: Control-1, Control-2, FR1, and FR2 groups. The control groups had free access to food, while the FR1 and FR2 groups experienced food deprivation for 12 h each day (7 pm to 7 am) over periods of 30 and 60 days, respectively. The average body weight of the mice was measured at the start and end of the study. The exploratory action, anxiety-like behaviors, and passive avoidance memory were evaluated using open field, elevated plus maze, and shuttle box devices. Histologic changes were assessed using H&E staining. The antioxidant capacity and alterations in gene expressions (BDNF and Inflammatory markers) were estimated in the hippocampus using FRAP methods and qRT-PCR, respectively. In young mice, 12-hour daily restricted feeding negatively affects cognitive, psychological, and exploratory behaviors. FR leads to a drop in antioxidant capacity, histological changes in the CA1 and CA3 regions, increased expression of inflammatory genes, and reduced BDNF expression. In summary, our outcome indicates that FR worsens brain oxidative stress, promotes inflammation in the brain, and eventually damages hippocampal neurons in young mice.