The 5:2 diet does not increase adult hippocampal neurogenesis or enhance spatial memory in mice

New neurones are generated throughout life in the mammalian brain in a process known as adult hippocampal neurogenesis (AHN). Since this phenomenon grants a high degree of neuroplasticity influencing learning and memory, identifying factors that regulate AHN may be important for ameliorating age-related cognitive decline. Calorie restriction (CR) has been shown to enhance AHN and improve memory, mediated by the stomach hormone, ghrelin. Intermittent fasting (IF), a dietary strategy offering more flexibility than conventional CR, has also been shown to promote aspects of AHN. The 5:2 diet is a popular form of IF; however, its effects on AHN are not well characterised. To address this, we quantified AHN in adolescent and adult wild-type and ghrelin-receptor-deficient mice following 6 weeks on a 5:2 diet. We report an age-related decline in neurogenic processes. However, the 5:2 diet does not increase AHN nor enhance memory performance, suggesting that this specific form of IF is ineffective in promoting brain plasticity to support learning. Synopsis Intermittent fasting, in the form of a 5:2 diet, does not induce hippocampal neurogenesis and learning in adolescent or adult mice of either sex. 5:2 diet does not increase AHN in adolescent or adult mice of either sex. 5:2 diet does not enhance spatial learning nor impact anxiety behaviour. Age significantly reduces AHN in adult mice.