Varying Dietary Component Ratios and Lingonberry Supplementation May Affect the Hippocampal Structure of ApoE–/– Mice

Abstract

ObjectiveThis study aimed to investigate and compare the morphological and biochemical characteristics of the hippocampus and the spatial memory of young adult ApoE–/– mice on a standard chow diet, a low-fat diet (LFD), a high-fat diet (HFD), and an HFD supplemented with lingonberries.MethodsEight-week-old ApoE–/– males were divided into five groups fed standard chow (Control), an LFD (LF), an HFD (HF), and an HFD supplemented with whole lingonberries (HF+WhLB) or the insoluble fraction of lingonberries (HF+InsLB) for 8 weeks. The hippocampal cellular structure was evaluated using light microscopy and immunohistochemistry; biochemical analysis and T-maze test were also performed. Structural synaptic plasticity was assessed using electron microscopy.ResultsApoE–/– mice fed an LFD expressed a reduction in the number of intact CA1 pyramidal neurons compared with HF+InsLB animals and the 1.6–3.8-fold higher density of hyperchromic (damaged) hippocampal neurons relative to other groups. The LF group had also morphological and biochemical indications of astrogliosis. Meanwhile, both LFD- and HFD-fed mice demonstrated moderate microglial activation and a decline in synaptic density. The consumption of lingonberry supplements significantly reduced the microglia cell area, elevated the total number of synapses and multiple synapses, and increased postsynaptic density length in the hippocampus of ApoE–/– mice, as compared to an LFD and an HFD without lingonberries.ConclusionOur results suggest that, in contrast to the inclusion of fats in a diet, increased starch amount (an LFD) and reduction of dietary fiber (an LFD/HFD) might be unfavorable for the hippocampal structure of young adult (16-week-old) male ApoE–/– mice. Lingonberries and their insoluble fraction seem to provide a neuroprotective effect on altered synaptic plasticity in ApoE–/– animals. Observed morphological changes in the hippocampus did not result in notable spatial memory decline.

A mixture of Nordic berries improves cognitive function, metabolic function and alters the gut microbiota in C57Bl/6J male mice

“…The study also found that the levels of synaptophysin and GluA1 were higher in the chow group compared to the HF group, which aligns with previous studies suggesting that high-fat diet feeding can induce synaptic plasticity and have a detrimental effect on synaptic efficiency ( 99 ). A significantly higher level of PSD95 in the HF group compared to the HF + berry seemed to be in contrast with a previous study showing that the consumption of lingonberry supplements significantly increased the total number of synapses and multiple synapses and increased postsynaptic density length in the hippocampus of ApoE–/– mice ( 100 ). However, as reported earlier by Martinsson et al ( 101 ), PSD95 protein levels do not always correlate with increased synapse density.…”

Maternal antibiotic administration during gestation can affect the memory and brain structure in mouse offspring

“…Structural synaptic plasticity was manually evaluated on electron micrographs of the hippocampus (at least 20/animal) by such parameters: number density of synapses and their different morphological types – simple, perforated, and multiple ones per 100 μm 2 of the stratum radiatum , as well as the postsynaptic density length. Synapses were categorized into morphological groups as previously described ( Shepilov et al, 2022 ), and their representative images are provided in Supplementary Figure 1 . To characterize myelination in the corpus callosum , the density of myelinated axons was quantified on at least 20 micrographs/animal (magnification x4800).…”

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“…Recent animal studies suggest that broad‐spectrum antibiotics can adversely affect fetal health by disrupting gut microbiota and metabolic pathways [231]. They also negatively impact neurodevelopment, including reduced neuron numbers in the hippocampus, smaller astrocytes, impaired neuron growth in the dentate gyrus, and loss of hippocampal synapses, potentially affecting early cognitive development in children [232]. Moreover, antibiotic treatment in pregnant mice can alter immune cell distribution, like increasing splenic Th1 cells and activated blood monocytes, while reducing Th2, Th17, and double‐positive FoxP3/RoRgT cells in the Peyer's patches and mesenteric lymph nodes, disrupting maternal immune regulation [233].…”