Sex-specific effects of ketogenic diet on anxiety-like behavior and neuroimmune response in C57Bl/6J mice

The ketogenic diet (KD) has been shown to reduce anxiety and enhance cognitive functions in neurological diseases. However, the sex-specific effects of KD on anxiety-like behavior in healthy individuals and the underlying molecular mechanisms contributing to these effects, including neuroinflammatio...

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Veröffentlicht in:The Journal of nutritional biochemistry 2024-05, Vol.127, p.109591, Article 109591
Hauptverfasser: Kumar, Mohit, Bhatt, Babita, Gusain, Chitralekha, Mahajan, Nayan, Bishnoi, Mahendra
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creator Kumar, Mohit
Bhatt, Babita
Gusain, Chitralekha
Mahajan, Nayan
Bishnoi, Mahendra
description The ketogenic diet (KD) has been shown to reduce anxiety and enhance cognitive functions in neurological diseases. However, the sex-specific effects of KD on anxiety-like behavior in healthy individuals and the underlying molecular mechanisms contributing to these effects, including neuroinflammation, are unelucidated. This study investigated the sex-specific effects of KD on anxiety-like behavior and the neuroimmune response in the prefrontal cortex (PFC) and hippocampus of healthy C57BL/6J male and female mice. Animals were fed either a control diet (CD- 17% fat, 65% carb, 18% protein) or a KD (80% fat, 5% carb, 15% protein) for 4 weeks. KD increased the levels of circulating β-hydroxybutyrate (BHB) both in males and females. However, PFC BHB levels were found to be elevated only in KD males. Moreover, KD did not affect the behavior of females but improved motor abilities and reduced anxiety levels in males. KD suppressed the mRNA expression of the pan microglial markers (Cd68, P2ry12) and induced morphological changes in the male PFC microglia. A sex-specific decrease in IL1β and an increase in IL-10 levels was found in the PFC of KD males. A similar trend was observed in the hippocampus of males where KD reduced the mRNA expression of P2ry12, Il1β, and cFos. Additionally, BHB increased the production of IL-10 whereas it decreased the production of IL1β from human microglia in in-vitro conditions. In summary, these results demonstrate that the anxiolytic and motor function enhancement abilities of KD are male-specific. Reduced pro-inflammatory and improved anti-inflammatory factors in the male PFC and hippocampus may underlie these effects. This is special type of abstract that is so short and could be inserted after main abstract of article, as a blurb or inserted as annotations into a Table of contents [Display omitted]
doi_str_mv 10.1016/j.jnutbio.2024.109591
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However, the sex-specific effects of KD on anxiety-like behavior in healthy individuals and the underlying molecular mechanisms contributing to these effects, including neuroinflammation, are unelucidated. This study investigated the sex-specific effects of KD on anxiety-like behavior and the neuroimmune response in the prefrontal cortex (PFC) and hippocampus of healthy C57BL/6J male and female mice. Animals were fed either a control diet (CD- 17% fat, 65% carb, 18% protein) or a KD (80% fat, 5% carb, 15% protein) for 4 weeks. KD increased the levels of circulating β-hydroxybutyrate (BHB) both in males and females. However, PFC BHB levels were found to be elevated only in KD males. Moreover, KD did not affect the behavior of females but improved motor abilities and reduced anxiety levels in males. KD suppressed the mRNA expression of the pan microglial markers (Cd68, P2ry12) and induced morphological changes in the male PFC microglia. A sex-specific decrease in IL1β and an increase in IL-10 levels was found in the PFC of KD males. A similar trend was observed in the hippocampus of males where KD reduced the mRNA expression of P2ry12, Il1β, and cFos. Additionally, BHB increased the production of IL-10 whereas it decreased the production of IL1β from human microglia in in-vitro conditions. In summary, these results demonstrate that the anxiolytic and motor function enhancement abilities of KD are male-specific. Reduced pro-inflammatory and improved anti-inflammatory factors in the male PFC and hippocampus may underlie these effects. 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A sex-specific decrease in IL1β and an increase in IL-10 levels was found in the PFC of KD males. A similar trend was observed in the hippocampus of males where KD reduced the mRNA expression of P2ry12, Il1β, and cFos. Additionally, BHB increased the production of IL-10 whereas it decreased the production of IL1β from human microglia in in-vitro conditions. In summary, these results demonstrate that the anxiolytic and motor function enhancement abilities of KD are male-specific. Reduced pro-inflammatory and improved anti-inflammatory factors in the male PFC and hippocampus may underlie these effects. 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subjects Anxiety
cognition
females
gene expression
hippocampus
humans
interleukin-10
ketogenic diet
Ketone bodies
males
neuroglia
Neuroinflammation
Precision nutrition
prefrontal cortex
Sex differences
tranquilizers
β-hydroxybutyrate
title Sex-specific effects of ketogenic diet on anxiety-like behavior and neuroimmune response in C57Bl/6J mice
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