Inhibition of mitochondrial fission attenuates Aβ-induced microglia apoptosis

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.

Keywords: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dipheny- ltetrazolium bromide; AD; Alzheimer’s disease; Aβ; BALB; Bagg albino; CytC; DMEM; Drp1; Dulbecco’s modified eagle medium; FBS; GTP; Guanosine triphosphate; HD; Huntington’s disease; MTT; Mdivi-1; PBS; PD; Parkinson’s disease; RT-PCR; Reverse transcription-PCR; Rh-123; TUNEL; apoptosis; cytochrome c; dynamin-related protein 1; fetal bovine serum; mdivi-1; microglia; mitochondrial division inhibitor 1; phosphate buffered saline; rhodamine 123; terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling; β-amyloid; β-amyloid protein.