Baicalin attenuates amyloid β oligomers induced memory deficits and mitochondria fragmentation through regulation of PDE-PKA-Drp1 signalling

Abstract

Rationale: Mitochondrial fragmentation contributes to the initiation of Alzheimer's disease (AD) pathology. Baicalin plays a significant role in rescuing mitochondrial dysfunction. However, the effect of baicalin treatment on the modulation of mitochondrial fragmentation has not yet been assessed.

Objectives: The present study was designed to evaluate the effect of baicalin on memory and understand its mechanism of action.

Results: Baicalin treatment significantly reversed the altered learning and memory behaviours in AD mouse model. We found that baicalin treatment significantly improved the levels of microtubule association protein-2 and enhanced the expression of synaptophysin and postsynaptic density protein 95 (PSD95). Moreover, treatment with baicalin reversed amyloid-β oligomer (AβO)-induced abnormalities in the succinate dehydrogenase complex iron sulphur subunit B (SDHB) and cytochrome c oxidase components I (COXI) and mitochondrial fragmentation in the hippocampus. Further, we found that baicalin decreased the PDE4 levels and upregulated the levels of phosphorylated Ser157 site of vasodilator-stimulated phosphoprotein (pVASP^s157) and phosphorylated Ser637 site of mitochondrial dynamin-related protein 1 (pDrp1^S637). Moreover, in AβO-treated HT-22 cells, H89 inhibited the effect of baicalin on PSD95, mitochondrial fragmentation, SDHB and COXI, PDE4, pVASP^s157, and pDrp1^S637.

Conclusion: The effect of baicalin on memory improvement may be due to improved synaptic plasticity, mitochondrial fragmentation, and rescue of dysfunction via the inhibition of PDE4, which leads to activation of pDrp1^S637 in the AβO-induced model.

Keywords: Alzheimer’s disease; Baicalin; Mitochondria fragmentation; PDE; PKA-pDrp1S637.