Evidence map›Paper›PMID 40660790›Full record

ArticleCNS neuroscience & therapeutics2025

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

Saleheh Mansouri Boutegaz, Mohammad Reza Namavar, Mehri Shadi, Hamid Kabiri-Rad, Saeed Vafaei-Nezhad

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Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Saleheh Mansouri BoutegazDepartment of Anatomical Sciences, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran.
Mohammad Reza NamavarHistomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.ORCID 0000-0002-6635-2717
Mehri ShadiDepartment of Anatomical Sciences, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran.ORCID 0000-0003-4368-2139
Hamid Kabiri-RadCellular & Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.
Saeed Vafaei-NezhadDepartment of Anatomical Sciences, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran.ORCID 0000-0003-0970-9334

Funding

Birjand University of Medical Sciences
6 · The paper itself

Abstract

backgroundGestational 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.

methodsForty 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.

resultsOffspring 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.

conclusionMaternal 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.

Indexed as

AutophagyDiabetes, GestationalDiabetes Mellitus, ExperimentalHippocampusNeuronsPrenatal Exposure Delayed EffectsAnimalsAnimals, NewbornFemaleInsulinPhosphatidylinositol 3-KinasesPregnancyRatsRats, WistarSignal TransductionTOR Serine-Threonine KinasesInsulinmTOR protein, ratPhosphatidylinositol 3-KinasesTOR Serine-Threonine Kinasesautophagygestational diabeteshippocampusspatial arrangementstreptozotocin

Identifiers

PMID40660790
PMCPMC12260216

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.