# Neurodevelopmental Consequences of Maternal Diabetes: Autophagy and Spatial Arrangement of Hippocampal Neurons

## TL;DR

Maternal diabetes harms neonatal brain development by disrupting hippocampal structure and autophagy, but insulin treatment can reduce these effects.

## Contribution

This study reveals how maternal diabetes affects hippocampal development and autophagy via the PI3K/mTOR pathway in neonatal rats.

## Key findings

- Maternal diabetes reduces hippocampal volume and increases neuronal damage in offspring.
- Insulin treatment during pregnancy mitigates hippocampal damage and preserves neural structure.
- The PI3K/mTOR pathway is upregulated in diabetic offspring, while ATG-7 is downregulated.

## Abstract

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder that disrupts fetal central nervous system (CNS) development. This study investigates the effects of maternal diabetes on hippocampal structure and autophagy‐related mechanisms in neonatal rats, focusing on the PI3K/mTOR signaling pathway.

Forty female Wistar rats were divided into three groups: control (CON), diabetic (STZ‐D), and insulin‐treated diabetic (STZ‐INS). Hyperglycemia was induced using streptozotocin, and offspring were analyzed at postnatal day 14 (P14). Histological evaluations of hippocampal structure were conducted using hematoxylin and eosin (H&E) staining, and neuronal damage was assessed with toluidine blue staining. Autophagy‐related gene expression (Beclin‐1, LC‐3, ATG‐7) and the PI3K/mTOR signaling pathway were examined using real‐time PCR.

Offspring from the STZ‐D group exhibited significant reductions in hippocampal volume and increased dark neurons in the CA1 and CA2 regions compared to the CON and STZ‐INS groups. Gene expression analysis revealed a marked downregulation of ATG‐7 and significant upregulation of PI3K and mTOR in the STZ‐D group, while Beclin‐1 and LC‐3 showed no significant changes. Insulin treatment mitigated these adverse effects, preserving hippocampal structure and reducing neuronal damage. In addition, the results of the Voronoi tessellation method showed that hippocampal neural cells depict a regular pattern in different subfields in all experimental groups.

Maternal hyperglycemia disrupts hippocampal development by altering autophagy and activating the PI3K/mTOR pathway, contributing to neuronal damage. Insulin treatment during pregnancy can counteract these effects, emphasizing the importance of glycemic control. These findings highlight potential therapeutic targets for mitigating CNS impairments in the offspring of diabetic mothers.

The study explores the impact of maternal diabetes on neonatal brain development, revealing significant weight reductions and alterations in brain structure, suggesting potential neurodevelopmental consequences and insulin treatment benefits.