MAM-Mediated Mitochondrial Ca2+ Overload and Endoplasmic Reticulum Stress Aggravates Synaptic Plasticity Impairment in Diabetic Mice
Jie Zhang, Jie Jiang, Haocong Li, Junliang Deng, Wei Dong, Huidan Deng
TL;DR
This study finds that high glucose causes mitochondrial and endoplasmic reticulum stress in diabetic mice, leading to impaired brain cell connections.
Contribution
The study identifies MAM-mediated mitochondrial Ca2+ overload and ER stress as novel mechanisms linking diabetes to synaptic plasticity impairment.
Findings
High glucose increases MAM number and activates endoplasmic reticulum stress in hippocampal neurons.
Blocking MAM Ca2+ transport or ER stress pathways protects against synaptic plasticity damage.
Knockdown of Mfn2 reverses high-glucose-induced mitochondrial and ER stress.
Abstract
Background: As a chronic threat to human and animal health, diabetes impairs cognition and synaptic plasticity through mechanisms that remain unresolved. This study aims to explore whether mitochondria-associated endoplasmic reticulum membrane (MAM)-mediated mitochondrial Ca2+ overload and endoplasmic reticulum stress plays an important role in high-glucose-induced synaptic plasticity damage in hippocampal neurons. Methods and Results: In diabetic mice, cognitive dysfunction was tightly linked to the synaptic plasticity impairment, manifesting as significant reductions in both mRNA and protein levels of PSD-95, GAP-43, and SYP. Concomitantly, aberrant increases in MAM number and structural alterations, along with pronounced up-regulation of Mfn2, were observed in hippocampal tissue from diabetic mice and cultured hippocampal neurons exposed to high glucose. High glucose also elevated…
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Taxonomy
TopicsMitochondrial Function and Pathology · Endoplasmic Reticulum Stress and Disease · Calpain Protease Function and Regulation