Mol Neurobiol. 2025 May 14. doi: 10.1007/s12035-025-05033-x. Online ahead of print.
ABSTRACT
The gestational diabetes mellitus (GDM) rat model was established through a combination of high-fat diet and streptozotocin. GDM is a common disease during pregnancy with high morbidity, which is associated with a high risk of neurological changes in the offspring. Neuroinflammation plays an important role in the development of anxiety-depression-like behavior. However, the mechanisms involved are unknown. This study aimed to investigate whether GDM induces chronic neuroinflammation in the offspring, resulting in anxiety-depression-like behavior. Our study used high-fat diets and streptozotocin to establish a gestational diabetes rat model. Eight-week-old offspring were assessed for anxiety-depression-like behavior using the open field test and the modified forced swimming test. Prefrontal cortex (PFC) tissue was observed by H&E staining. The expression level of peripheral and central inflammation was monitored by ELISA. Differentially expressed genes in the PFC were detected by RNA-sequencing. The results of RNA-sequencing were verified by RT-qPCR, Western blot, and Wes™ Automatic Western Blot Quantitative Analysis. Anxiety-depression-like behavior was observed in the offspring of GDM. It indicated that PFC neurons were impaired and neuroinflammation was more serious in the GDM offspring, in which the increased concentration of CXCL10 was observed. Moreover, it revealed that the PI3K/AKT pathway was enriched by KEGG analysis. Mechanistically, GDM increased astrocyte activation and facilitated the nuclear translocation of phosphorylated-nuclear factor-κ B (p-NF-κB) in the offspring. The development of anxiety-depression-like behavior in the offspring of GDM rats was influenced by neuroinflammation in the PFC. These effects may be associated with astrocyte activation and activation of the NF-κB pathway.
PMID:40360956 | DOI:10.1007/s12035-025-05033-x