Maternal Low-Protein Diet Induces Sex-Specific Alterations in Hippocampal Glial Fibrillary Acidic Protein Expression
Paola Cristina Bello-Medina1, Mauricio Díaz-Muñoz2, Jonathan Rafael Trinidad-Gallardo3
1Departamento de Biología, Facultad de Ciencias, Universidad del Tolima, Altos de Santa Helena, Ibagué, Tolima, Colombia.
Insights
Maternal low-protein diet during pregnancy causes sex-specific hippocampal changes in male pups, increasing glial fibrillary acidic protein (GFAP) and cell density. Female pups showed no significant alterations, indicating males
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Maternal nutrition is vital for fetal brain development.
- Low-protein isocaloric diets (LPID) may negatively impact cognition.
- Sex-specific effects of maternal LPID on early hippocampal development are not well understood.
Purpose of the Study:
- To investigate the sex-specific effects of maternal LPID on hippocampal maturation.
- To examine alterations in astrocytic activation and cell density in male and female pups.
Main Methods:
- Pregnant Wistar rats were fed either a control or LPID diet.
- Pups were analyzed on postnatal day 10 (PND10) using immunohistochemistry.
- Glial fibrillary acidic protein (GFAP) and DAPI staining were employed to assess astrogliosis and cell density.
Main Results:
- Maternal LPID induced sex-specific changes, primarily in male pups.
- Male pups exhibited significant GFAP upregulation in CA1 hippocampal subregions.
- Increased cell density was observed in CA1, CA3, and dentate gyrus of male pups, with no significant changes in females.
Conclusions:
- Maternal LPID during early development causes sex-specific hippocampal astrogliosis in male offspring.
- This nutritional insult disrupts cellular organization exclusively in males.
- Male pups demonstrate increased vulnerability to early-life nutritional stress.
Background:
Maternal nutrition during pregnancy and lactation is crucial for pup brain development. A low-protein isocaloric diet (LPID) has been associated with cognitive deficits, but its sex-specific effects on early hippocampal maturation remain unclear. This study examined whether maternal LPID alters astrocytic activation, measured by glial fibrillary acidic protein (GFAP) expression and cell density, in hippocampal subregions of male and female pups on postnatal day 10 (PND10).
Method:
Pregnant Wistar rats were fed either a control diet (18% protein) or an LPID (6% protein) throughout gestation and lactation. The pups' brains were analyzed via immunohistochemistry using GFAP and 4',6-diamidino-2-phenylindole (DAPI) staining.
Results:
Maternal LPID caused sex-specific changes limited to male pups. These showed marked GFAP upregulation in the CA1 pyramidal and radiatum layers, with increases of up to 225% compared to females and 124% compared to controls. DAPI staining revealed higher cell density in CA1 (up to +34%), CA3 (+34%), and the dentate gyrus (+45%), respectively. The hilus showed a 71% increase compared to females. No significant differences were observed in LPID females across hippocampal regions.
Conclusion:
These findings suggest that maternal LPID during early development induces hippocampal astrogliosis, evidenced by increased GFAP expression, in a sex-specific manner. This process disrupts cellular organization exclusively in males, which highlights their increased vulnerability to early-life nutritional stress.


