Abstract
BackgroundThe aim of the present study was to investigate the effects of Scutellaria barbata flavonoids (SBF) on memory impairment and neuronal injury induced by amyloid beta protein 25–35 in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1 (RHTGF-β1) (composited Aβ) in rats.MethodsThe composited Aβ-treated model of Alzheimer’s disease (AD)-like memory impairment and neuronal injury was established in male rats by right intracerebroventricular injection of composited Aβ, and the effects of SBF were assessed using this rat model. Spatial learning and memory of rats were assessed in the Morris water maze, and neuronal injury was assessed by light and electron microscopy with hematoxylin-eosin or uranyl acetate and lead nitrate-sodium citrate staining, respectively.ResultsIn the Morris water maze, memory impairment was observed in 94.7% of the composited Aβ-treated rats. The composited Aβ-treated rats took longer than sham-operated rats to find the hidden platform during position navigation and reversal learning trials. They also spent less time swimming in the target quadrant in the probe trial. Optical and electron microscopic observations showed significant neuropathological changes including neuron loss or pyknosis in hippocampus, typical colliquative necrosis in cerebral cortex, mitochondrial swelling and cristae fragmentation and a large number of lipofuscin deposits in the cytoplasm. Treatment with SBF (35–140 mg/kg) reduced the memory impairment and neuronal injury induced by composited Aβ.ConclusionSBF-mediated improvement of composited Aβ-induced memory impairment and neuronal injury in rats provides an appropriate rationale for evaluating SBF as a promising agent for treatment of AD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12993-016-0118-8) contains supplementary material, which is available to authorized users.
Highlights
The aim of the present study was to investigate the effects of Scutellaria barbata flavonoids (SBF) on memory impairment and neuronal injury induced by amyloid beta protein 25–35 in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1 (RHTGF-β1) in rats
Screening Alzheimer’s disease (AD) model rats using the Morris water maze test In recording adaptive swimming, we found that the sham-operated rats always swam freely, and the composited Aβ-treated rats always swam around the pool perimeter (Fig. 2a)
When the screening ratio (SR), which was based on the latency to find the hidden platform on day 4 for composited Aβ-treated and sham-operated rats, was more than 0.2, this animal was considered as a successful model rat
Summary
The aim of the present study was to investigate the effects of Scutellaria barbata flavonoids (SBF) on memory impairment and neuronal injury induced by amyloid beta protein 25–35 in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1 (RHTGF-β1) (composited Aβ) in rats. Multiple neurotoxic events in the brain, such as Aβ aggregation, tau protein hyperphosphorylation, disruption of calcium homeostasis, and production of reactive oxygen species, have been shown to occur when animals were intraventricularly injected with Aβ [3]. The deposited Aβ may result in massive SP and NFT formation, and the combined effects of deposited Aβ and hyperphosphorylated tau protein exacerbate neurotoxicity and advance dementia [4].
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