Paternal Prenatal and Lactation Exposure to a High-Calorie Diet Shapes Transgenerational Brain Macro- and...

Area of Science:

• Neuroscience
• Developmental Biology
• Behavioral Science

Background:

• Prenatal exposure to high-energy diets (HED) is linked to increased susceptibility to behavioral alterations in male offspring.
• The potential for transgenerational inheritance of these HED-induced changes, particularly structural brain alterations impacting anxiety and depression, remains an area of investigation.

Purpose of the Study:

• To investigate whether prenatal HED exposure primes the transgenerational inheritance of structural brain changes that impact anxiety- and depression-like behavior in male offspring.
• To assess these effects across multiple filial generations (F1, F2, and F3).

Main Methods:

• Female Wistar rats were exposed to either a HED (cafeteria diet) or a control (chow) diet during development.
• Anxiety and depression-like behaviors were evaluated in male offspring (F1, F2, F3) using standard behavioral tests (OFT, EPM, NSFT, TST, FST).
• Structural brain changes were analyzed using deformation-based morphometry (DBM) and diffusion tensor imaging (DTI) via ex vivo MRI.

Main Results:

• Offspring exposed to the HED exhibited higher anxiety-like behaviors across F1, F2, and F3 generations, including longer feeding latencies in the NSFT.
• DBM revealed altered brain volumes in the cerebellum, hypothalamus, amygdala, and hippocampus in HED offspring, persisting up to the F3 generation.
• F3 HED offspring showed altered white matter integrity in the amygdala and hippocampus (increased fractional anisotropy and axial diffusivity) and corpus callosum (increased apparent diffusion coefficient).

Conclusions:

• Prenatal and lactation exposure to HED programs the transgenerational inheritance of structural brain changes.
• These neuroanatomical alterations are associated with anxiety-like behavior in male offspring, persisting across generations.
• The findings underscore the long-term impact of maternal diet on neurodevelopment and behavior with potential transgenerational implications.