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Inhibition of mitochondrial fission attenuates Aβ-induced microglia apoptosis
1Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Abstract:
Mitochondrial division inhibitor 1 (mdivi-1), a selective inhibitor of mitochondrial fission protein dynamin-related protein 1 (Drp1), has been reported to display neuroprotective properties in different animal models. In the present study, we investigated the protective effect of mdivi-1 on β-amyloid protein (Aβ)-induced cytotoxicity and its potential mechanisms in BV-2 and primary microglial cells. We found that mitochondrial fission was increased in Aβ treatment and inhibition of mitochondrial fission by mdivi-1 significantly reduced Aβ-induced expression of CD11b (a marker of microglial activation), viability loss and apoptotic rate increase in BV-2 and primary microglial cells. Moreover, we also found that mdivi-1 treatment markedly reversed mitochondrial membrane potential loss, cytochrome c (CytC) release and caspase-3 activation. Altogether, our data suggested that mdivi-1 exerts neuroprotective effects against Aβ-induced microglial apoptosis, and the underlying mechanism may be through inhibiting mitochondrial membrane potential loss, CytC release and suppression of the mitochondrial apoptosis pathway.
Insights
Mitochondrial division inhibitor 1 (mdivi-1) protects microglial cells from beta-amyloid toxicity by inhibiting mitochondrial fission and apoptosis. This suggests mdivi-1 as a potential therapeutic for neurodegenerative diseases involving microglial dysfunction.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Mitochondrial dynamics, particularly fission, are implicated in neuroinflammation.
- Beta-amyloid (Aβ) protein accumulation triggers microglial activation and contributes to neurodegenerative processes.
- Mitochondrial division inhibitor 1 (mdivi-1) is known to inhibit dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and exhibits neuroprotective effects.
Purpose of the Study:
- To investigate the protective effects of mdivi-1 against Aβ-induced cytotoxicity in microglial cells.
- To elucidate the underlying mechanisms of mdivi-1's action, focusing on mitochondrial pathways.
Main Methods:
- BV-2 and primary microglial cells were treated with Aβ.
- Mitochondrial fission was assessed, and cells were treated with mdivi-1.
- Microglial activation marker (CD11b), cell viability, and apoptosis rates were measured.
- Mitochondrial membrane potential, cytochrome c (CytC) release, and caspase-3 activation were analyzed.
Main Results:
- Aβ treatment increased mitochondrial fission, CD11b expression, viability loss, and apoptosis in microglial cells.
- Mdivi-1 treatment significantly reduced Aβ-induced CD11b expression, viability loss, and apoptosis.
- Mdivi-1 reversed Aβ-induced mitochondrial membrane potential loss, CytC release, and caspase-3 activation.
Conclusions:
- Mdivi-1 exerts significant neuroprotective effects against Aβ-induced microglial apoptosis.
- The protective mechanism involves the inhibition of mitochondrial fission, preservation of mitochondrial membrane potential, and suppression of the mitochondrial apoptosis pathway.
