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

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.

Early- but not late-adolescent Western diet consumption programs for long-lasting memory impairments in male but not female rats

“…These results indicate that a 1-week window from PN 21-28 is insufficient to impart long-lasting memory impartments, even in males. These findings align with the reversible impacts of HFD (60% kcal from fat) exposure for 1 week (PN 35-42) on hippocampal DCX + structure and BDNF expression in rats found by Chiazza et al (2021). Khazen and colleagues (2019) examined whether 1-week juvenile (PN 21-28) vs. adult (PN 60-67) consumption of a HFD (60% kcal from fat) vs. control diet (4% kcal from fat) affected HPC-dependent memory function in male Sprague Dawley rats.…”

“…For example, sugar-enriched high-fat diet (HFD) consumption during the entire adolescent period in rats reduces hippocampal neurogenesis and impairs spatial memory (Boitard et al, 2016). That there may be critical vulnerable windows of development within the adolescent period is suggested by results showing that 1-week HFD consumption from postnatal days (PN) 35-42, which loosely corresponds to mid-adolescence, disrupts doublecortin + (DCX + ) structure and reduces brain-derived neurotrophic factor (BDNF) expression in the HPC, which are markers of newly proliferated neurons and neural plasticity, respectively (Chiazza et al, 2021). However, these changes were shown to be largely reversed with a 1-week washout on a low-fat diet (Chiazza et al, 2021).…”

Expression and Significance of Transforming Growth Factor-Beta/Smad Pathway in the Prefrontal-Hippocampal Loop in Rats with Cognitive Impairment Associated with Alcohol Dependence

“…In a study based on a stereological system, it was observed that chronic alcohol consumption resulted in reduced prefrontal and anterior cingulate volumes, reduced prefrontal mean neuronal volume and reduced total neuronal volume in rats [25] . Adolescent rats fed with HFD and alcohol showed astrogliosis in the granular layer of the dentate gyrus of the hippocampus and a decrease in the number of mature neuronal cells in the CA3 region [26,27] . Under the same conditions, both the area and volume of the cerebellum became smaller, alcohol consumption had the greatest effect on the cerebellar vermis and smaller cerebellar measurements were positively associated with poorer performance in cognitive performance [28] .…”

Feeding the Brain: Effect of Nutrients on Cognition, Synaptic Function, and AMPA Receptors

“…Mixed and saturated HFD-induced impairment is also associated with changes in other neuroplasticity-related factors, such as decreased BDNF [ 93 , 95 , 97 , 106 , 113 , 115 , 123 ]. The fact that acute exposure to an HFD leads to changes in BDNF levels suggests that the alterations may be a direct cause of glutamatergic synaptic dysfunction.…”