Title:Atorvastatin Calcium Ameliorates Cognitive Deficits Through the AMPK/Mtor Pathway in Rats with Vascular Dementia
Volume: 27
Issue: 1
Author(s): Xiuqin Li, Shaopeng Chen, Guiming Zheng, Yanyan Yang, Nan Yin, Xiaoli Niu, Lixia Yao and Peiyuan Lv*
Affiliation:
- Department of Neurology, Hebei Medical University, Shijiazhuang, Hebei, 050017, China.
- Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, 050051, China.
Keywords:
Atorvastatin calcium (AC), vascular dementia (VD), cognitive deficits, autophagy, apoptosis, AMPK/mTOR pathway.
Abstract:
Aim: In this study, the protective effects of atorvastatin calcium (AC) on nerve cells and
cognitive improvement in vivo and in vitro were investigated by establishing cell models and vascular
dementia (VD) rat models.
Background: VD is a neurodegenerative disease characterized by cognitive deficits caused by
chronic cerebral hypoperfusion. AC has been studied for its potential to cure VD but its efficacy
and underlying mechanism are still unclear.
Objective: The mechanism of action of AC on cognitive deficits in the early stages of VD is unclear.
Here, the 2-vessel occlusion (2-VO) model in vivo and the hypoxia/reoxygenation (H/R) cell
model in vitro was established to investigate the function of AC in VD.
Methods: The spatial learning and memory abilities of rats were detected by the Morris method.
The IL-6, tumour necrosis factor-α (TNF-α), malondialdehyde (MDA) and superoxide dismutase
(SOD) in cell supernatant was tested by ELISA kits. After behavioural experiments, rats were
anaesthetized and sacrificed, and their brains were extracted. One part was immediately fixed in
4% paraformaldehyde for H&E, Nissl, and immunohistochemical analyses, and the other was
stored in liquid nitrogen. All data were shown as mean ± SD. Statistical comparison between the
two groups was performed by Student’s t-test. A two-way ANOVA test using GraphPad Prism 7
was applied for escape latency analysis and the swimming speed test. The difference was considered
statistically significant at p < 0.05.
Results: AC decreased apoptosis, increased autophagy, and alleviated oxidative stress in primary
hippocampal neurons. AC regulated autophagy-related proteins in vitro by western blotting. VD
mice improved cognitively in the Morris water maze. Spatial probing tests showed that VD animals
administered AC had considerably longer swimming times to the platform than VD rats.
H&E and Nissl staining showed that AC reduces neuronal damage in VD rats. Western blot and
qRT-PCR indicated that AC in VD rats inhibited Bax and promoted LC3-II, Beclin-1, and Bcl-2 in
the hippocampus region. AC also improves cognition via the AMPK/mTOR pathway.
Conclusion: This study found that AC may relieve learning and memory deficits as well as neuronal
damage in VD rats by changing the expression of apoptosis/autophagy-related genes and activating
the AMPK/mTOR signalling pathway in neurons.
