# Neurodevelopmental Changes in the Guinea Pig Brain Caused by Time-Limited Complete Vitamin C Deprivation

## TL;DR

This study shows that vitamin C deprivation in guinea pigs during specific developmental periods causes brain abnormalities, including bleeding and structural defects.

## Contribution

The study identifies specific neurodevelopmental effects of vitamin C deficiency during distinct gestational periods in guinea pigs.

## Key findings

- Cerebral bleeding and porencephaly were observed in guinea pigs deprived of vitamin C from the 10th day of gestation.
- Decreased expression of collagen-related genes was found in the cerebellum of guinea pigs deprived of vitamin C from the 20th day.
- Microscopic analysis revealed neuron loss and dysplastic changes in the cerebellum of vitamin C-deprived guinea pigs.

## Abstract

Background/Objectives: The guinea pig is a unique experimental model because of the evolutionary loss of the GULO gene, which encodes an enzyme involved in vitamin C synthesis. Since vitamin C plays an essential role in collagen biochemistry, numerous studies have investigated the effects of pre- and postnatal vitamin C deficiency. However, only a few studies, including ours, have indicated a possible link between vitamin C deprivation and potential weakening of the basement membrane, which may lead to significant alterations in brain structure. Methods: The experiment included guinea pig foetuses completely deprived from the 10th (E2 group) and the 20th (E1 group) to the 50th day of intrauterine life. Tissue samples from the cerebrum and cerebellum were taken for biochemical, molecular, and immunohistochemical analyses. Results: In the E2 group alone, we found marked gross changes: cerebral bleeding, porencephaly, and a lissencephalic cerebellar surface. Microscopic examination revealed diffuse bleeding in the cerebrum along with a loss of neurons in the area of the defect, specifically in the E2 group. The complete maturation of ectopic neurons characterised dysplastic changes in the cerebellum. Hydroxyproline analysis of both the cerebrum and cerebellum showed no significant differences among the E1, E2, and control groups. However, decreased expression of COL1, COL4A1, and SLC23A1 was observed solely in the cerebellar tissue of the E1 group. Conclusions: The morphological, biochemical, and molecular results represent preliminary associations with vitamin C deficiency, but require further validation.