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bioRxiv · 10.1101/2022.10.03.510613

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

Roberts, L. D.·Hornsby, A. K. E.·Thomas, A.·Sassi, M.·Kinzett, A.·Hsiao, N.·David, B. R.·Good, M.·Wells, T.·Davies, J. S.
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Abstract

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 and mood related behaviour, identifying factors that regulate AHN may be important for ameliorating age-related cognitive decline and neurodegeneration. Calorie restriction (CR), in the absence of malnutrition, has been shown to enhance AHN and improve hippocampal-dependent memory, mediated by the stomach hormone, ghrelin. Intermittent fasting (IF), a dietary strategy offering more flexibility than conventional CR, also promotes aspects of AHN. The 5:2 diet is a popular form of IF linked to a range of health benefits, however its effects on AHN and spatial memory are not well characterised. We hypothesised that the 5:2 diet would enhance AHN in a ghrelin-dependent manner. To assess this, we used immunohistochemistry to quantify new adult-born neurones and new neural stem cells (NSCs) in the hippocampal DG of adolescent and adult wild-type and mice lacking the ghrelin receptor following six weeks on a 5:2 diet. We report an age-related decline in neurogenic processes and identify a novel role for ghrelin-receptor in regulating the formation of new adult born NSCs in an age-dependent manner. However, the 5:2 diet did not affect new neurone or NSC formation in the DG. Consistent with this finding the 5:2 diet did not alter performance on a spatial learning and memory task. These data suggest that the 5:2 diet used in this study does not increase AHN or improve associated spatial memory function. HighlightsO_LI5:2 diet does not increase adult hippocampal neurogenesis C_LIO_LI5:2 diet does not enhance spatial memory performance C_LIO_LIThere is an age-related decline in adult hippocampal neurogenesis C_LIO_LIGhrelin-receptor regulates new neural stem cell and new neurone number in an age-related manner C_LIO_LIGhrelin-receptor is required for intact spatial memory C_LI

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Roberts, L. D., Hornsby, A. K. E., Thomas, A., Sassi, M., Kinzett, A., Hsiao, N., David, B. R., Good, M., Wells, T., Davies, J. S.. 2022-10-06. The 5:2 diet does not increase adult hippocampal neurogenesis or enhance spatial memory in mice. https://doi.org/10.1101/2022.10.03.510613

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