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Mechanism of Kaixinsan on Learning and Memory Ability and Synaptic Function of APP/PS1 Mice / 中国实验方剂学杂志
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 15-22, 2021.
Article in Chinese | WPRIM | ID: wpr-906076
ABSTRACT

Objective:

To explore the underlying protective mechanism of Kaixinsan on learningmemory, and synaptic function in APP/PS1 mice.

Method:

Sixty APP/PS1 mice were randomly divided into a model group, a donepezil (2 mg·kg<sup>-1</sup>·d<sup>-1</sup>) group, and low- (0.7 g·kg<sup>-1</sup>·d<sup>-1</sup>), medium- (1.4 g·kg<sup>-1</sup>·d<sup>-1</sup>), and high-dose (2.8 g·kg<sup>-1</sup>·d<sup>-1</sup>) Kaixinsan groups, and the wild-type mice of the same age in the same litter were assigned to the normal group, with 12 mice in each group. After continuous intragastric administration for two months, the Morris water maze experiment was performed. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The colorimetric assay was used to detect serum content of acetylcholine (ACh), choline acetyltransferase (ChAT), acetylcholinesteraseAChE), and levels of hippocampal reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Real-time fluorescence-based quantitative polymerase chain reaction (Real- time PCR) was used to detect the mRNA expression of hippocampal brain-derived neurotrophic factorBDNF), beta-nerve growth factor (NGFB), discs large homolog (DLG)2, DLG4, and synaptophysin (SYP).

Result:

Compared with the normal group, the model group showed prolonged escape latency, reduced number of crossing platforms, shortened stay in the target quadrant (<italic>P</italic><0.01), decreased number of mitochondria with different shapes and irregular arrangement, some swollen and deformed mitochondria with broken mitochondrial cristae, endolysis, and cytoplasm vacuole, and more cell debris. Additionally, the model group also displayed reduced serum levels of ACh and ChAT, increased AChE (<italic>P</italic><0.01), elevated hippocampal ROS and MDA (<italic>P</italic><0.05,<italic>P</italic><0.01), declining SOD and GSH-Px (<italic>P</italic><0.01), and diminished hippocampal BDNF, NGFB, DLG2, DLG4, and SYP mRNA levels (<italic>P</italic><0.05,<italic>P</italic><0.01). Compared with the model group, the donepezil group, and the medium- and high-dose Kaixinsan groups showed shortened escape latency, increased number of crossing platforms, prolonged stay in the target quadrant (<italic>P</italic><0.05,<italic>P</italic><0.01), improved mitochondrial damage with a regular shape (mainly oval shape), relieved mitochondrial swelling and deformation, and clear mitochondrial cristae. Furthermore, the donepezil group, and the medium- and high-dose Kaixinsan groups also exhibited increased serum ACh and ChAT levels (<italic>P</italic><0.05,<italic>P</italic><0.01), blunted AChE activity (<italic>P</italic><0.05), reduced hippocampal ROS level (<italic>P</italic><0.05,<italic>P</italic><0.01), declining MDA level (<italic>P</italic><0.05), potentiated SOD and GSH-Px activities, and up-regulated hippocampal BDNF, NGFB, DLG2, DLG4, and SYP mRNA levels (<italic>P</italic><0.05,<italic>P</italic><0.01). In the low-dose Kaixinsan group, the stay time in the target quadrant was prolonged and the expression of hippocampal SYP mRNA was elevated significantly (<italic>P</italic><0.05). There was no statistical difference in swimming speed between the groups.

Conclusion:

Kaixinsan can improve the learning and memory ability of APP/PS1 mice by increasing the expression of synaptic plasticity-related proteins, reducing the ultrastructural damage to hippocampal neurons, resisting oxidative stress, and regulating cholinergic neurotransmitters, thereby exerting neuroprotective effects.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article