Short high fat diet triggers reversible and region specific effects in DCX+ hippocampal immature neurons of adolescent male mice

Fausto Chiazza,Pier Luigi Canonico,Mariagrazia Grilli,Federico Ugazio,Valeria Bortolotto,Heather Bondi,Irene Masante

doi:10.1038/s41598-021-01059-y

Fausto Chiazza, Pier Luigi Canonico + Show 5 more

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https://doi.org/10.1038/s41598-021-01059-y

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Abstract

Adolescence represents a crucial period for maturation of brain structures involved in cognition. Early in life unhealthy dietary patterns are associated with inferior cognitive outcomes at later ages; conversely, healthy diet is associated with better cognitive results. In this study we analyzed the effects of a short period of hypercaloric diet on newborn hippocampal doublecortin+ (DCX) immature neurons in adolescent mice. Male mice received high fat diet (HFD) or control low fat diet (LFD) from the 5th week of age for 1 or 2 weeks, or 1 week HFD followed by 1 week LFD. After diet supply, mice were either perfused for immunohistochemical (IHC) analysis or their hippocampi were dissected for biochemical assays. Detailed morphometric analysis was performed in DCX+ cells that displayed features of immature neurons. We report that 1 week-HFD was sufficient to dramatically reduce dendritic tree complexity of DCX+ cells. This effect occurred specifically in dorsal and not ventral hippocampus and correlated with reduced BDNF expression levels in dorsal hippocampus. Both structural and biochemical changes were reversed by a return to LFD. Altogether these studies increase our current knowledge on potential consequences of hypercaloric diet on brain and in particular on dorsal hippocampal neuroplasticity.

Highlights

Adolescence represents a crucial period for maturation of brain structures involved in cognition
In the suprapyramidal blade of the dentate gyrus (DG), we selected thirty DCX+ immature neurons with their cell body located in the inner third of the granular cell layer (GCL) and a dendritic tree reaching the molecular layer (ML)
We initially evaluated the effects of low fat diet (LFD) and high fat diet (HFD) on D CX+ immature neurons in the dorsal DG

Summary

Introduction

Adolescence represents a crucial period for maturation of brain structures involved in cognition. Recent experimental evidence in murine models showed that the number of DCX+ cells is reduced by chronic periods of o vernutrition[19,20], and these deleterious effects have a higher magnitude at younger a ges[21], and may be region-specific[22] Some of these alterations occur before a significant weight gain[24,25,26,27,28]. These findings suggest that overnutrition may directly affect brain structures, independently of metabolic derangements Based on these observations and in light of the potential relevance in pathophysiology, we investigated the effects of a short period of a HFD on the fine structural architecture of hippocampal DCX+ immature neurons in adolescent mice

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