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Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
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High-Fat Diet Alters Behavior and Hippocampal Gene Expression.

Melissa S Totten1, Ava L Peterson1, Derek M Pierce2

  • 1Chemistry, Biochemistry, and Nutrition Program, Salem College, Winston-Salem, NC 27101, USA.

International Journal of Molecular Sciences
|September 27, 2025
PubMed
Summary
This summary is machine-generated.

High-fat diets alter behavior and brain gene expression, with male mice of specific strains showing the greatest impact. Sex and genetics significantly influence diet-related changes in the brain.

Keywords:
alpha synucleinamyloid precursor proteinanxietybrainbrain-derived neurotrophic factorgene expressionhigh-fat diethippocampusmemoryobesity

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Area of Science:

  • Neuroscience
  • Dietary Science
  • Genetics

Background:

  • High-fat diets (HFD) are associated with altered gene expression and behavioral changes.
  • Understanding the influence of sex and genetic background is crucial for diet-related health outcomes.

Purpose of the Study:

  • To investigate the effects of a HFD on behavior and hippocampal gene expression.
  • To evaluate sex and genetic differences in response to HFD in mice.

Main Methods:

  • Male and female C57BL/6J (B6J) and DBA/2J (D2J) mice were fed a control or HFD for 16 weeks.
  • Behavioral tests included open field, nestlet shredding, and novel object recognition.
  • mRNA expression of alpha synuclein (αSYN), amyloid precursor protein (APP), and brain-derived neurotrophic factor (BDNF) was measured.

Main Results:

  • HFD reduced nestlet shredding in male B6J mice and increased fecal boli in HFD male B6Js.
  • No significant memory differences were observed.
  • Significant diet-sex-strain interactions for αSYN and APP mRNA; HFD upregulated αSYN (7-fold) and APP (10-fold) in male B6J hippocampi.
  • BDNF expression showed strain-sex interactions but no diet effect.

Conclusions:

  • HFD significantly impacts male B6J mice's behavior and hippocampal gene expression.
  • Biological sex and genetic background are critical factors in diet-induced brain changes.
  • Dietary interventions should consider individual genetic and sex-specific responses.