Mesenchymal Stem Cells Restore Endothelial Integrity and Alleviate Emotional Impairments in a Diabetic Mouse Model via Inhibition of MMP-9 Activity

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3355 - 3355

Published: April 3, 2025

Diabetes mellitus (DM) has reached pandemic prevalence, significantly impacting global health. Accumulating evidence highlighted a bidirectional relationship between diabetes and depression, with blood-brain barrier (BBB) disruption playing pivotal role in the pathogenesis of therapeutic approaches to both disorders. Mesenchymal stem cells (MSCs) have emerged as promising cell-based strategy for DM; however, their potential mitigate DM-associated emotional deficits remains unclear. This study investigates whether MSCs can restore BBB integrity improve diabetic mouse model via matrix metalloprotein-9 (MMP-9) inhibition. We used biochemical, molecular, behavioral analyses assess function, inflammation, behavior. Our results demonstrated that conditions induce dysfunction, characterized by MMP-9-mediated degradation tight junction (TJ) proteins claudin-5 (Cldn5) occludin (Ocln), alongside neuroinflammation impairments. Notably, MSC administration restored attenuated suppressing MMP-9 activity upregulating TJ proteins. Importantly, treatment not only alleviated anxiety- depressive-like behaviors but also enhanced glycemic control DMmodels. These findings elucidate mechanistic basis therapy DM-related neuropsychiatric complications and, crucially, reveal its dual efficacy concurrently ameliorating symptoms metabolic dysfunction DM models. synergistic effect provides translational rationale advancing MSC-based therapies into clinical applications.

Language: Английский

Type 2 diabetes mellitus, cerebral small vessel disease and depressive disorders

INTERNATIONAL NEUROLOGICAL JOURNAL, Journal Year: 2025, Volume and Issue: 21(3), P. 226 - 237

Published: May 20, 2025

Patients with type 2 diabetes mellitus (T2DM) have a significantly higher risk of developing depressive disorders compared to individuals without impaired carbohydrate metabolism. In the context population aging and increasing prevalence T2DM, there is an urgent need better understand mechanisms that determine relationship between brain disease. Depressive T2DM often share genetic, behavioral, psychosocial factors. However, it still unclear whether depression associated increased wide range cardiovascular diseases in patients metabolic biomarkers may mediate these associations. Existing scales for assessing demonstrate insufficient accuracy prediction, which prompts search new, more objective markers, one arterial stiffness. Cognitive impairment are likely different underlying pathophysiological mechanisms. common be microvascular dysfunction, namely cerebral small vessel disease (CSVD). Signs CSVD progress linearly development condition, from physiological state glucose metabolism prediabetes correlates glycemic levels even at stage prediabetes. There hypothesis serve as early determinant mechanism disorders, especially among elderly patients. data on stiffness comorbid remain limited. The aim this review was discuss specifics relationships disease, stiffness, well analyze new trends directions future research. conducted Scopus, Science Direct (from Elsevier) PubMed, including MEDLINE, databases. keywords used were “diabetes mellitus”, “cerebral disease”, “arterial stiffness”, “depressive disorders.” A manual bibliography publications identify research results could not found during online search.

Language: Английский