[Effects of huannao yicong formula extract on behavior and ultrastructure of hippocampus mitochondria of APP transgenic mice of different months].
OBJECTIVE
To study the effects of Huannao Yicong formula (HNYCF) extract on behavior and ultrastructure of mitochondria in hippocampus CA1 area of APP transgenic mice of different months, and explore its partial mechanism in treating Alzheimer's disease (AD) through the perspective of energy metabolism.


METHODS
One hundred and twenty APP695V717I transgenic mice of 3-month old were divided randomly into model group, Donepezil group (0.65 x 10(-3) g x kg(-1) x d(-1)), HNYCF extract large dose group (2.8 g x kg(-1) x d(-1)) and HNYCF extract small dose group (1.4 g x kg(-1) x d(-1)), and 30 mice in each group. Another 30 C57BL/6J mice with the same age and background were used as normal control group. All animals were administered once daily by gavage with the corresponding drug or distilled water. The course of intervention was 4 and 6 months. Behavioral changes were observed by Morris water maze test and step down test. Ultrastructure of mitochondria in hippocampus CA1 area was observed by transmission electron microscope.


RESULTS
At the age of 7 and 9 month, the number of times of passing through platform, swimming time and path length of model group increased significantly (P < 0.05, P < 0.01) in Morris water maze test, and the latent period decreased (P < 0.01) in step down test compared with normal group, and it would get worse with the development of disease course. HNYCF extract could increase the number of times of passing through platform, swimming time and path length (P < 0.05, P < 0.01) in Morris water maze test, prolong latent period in step down test of different age. At the age of 7 and 9 month, mitochondrial of hippocampus CA1 area was disrupted and dissolved. Most ridge structure arranged in a mess, and some ridge showed expanding, matrix loosing and swollen appearance, and it would get worse with the development of disease course. HNYCF extract could improve ultrastructure of mitochondria in hippocampus CA1 area, and increase its quality.


CONCLUSIONS
Learning and memory ability decreased in APP transgenic mice model, and the quantity of neural mitochondria in hippocampus CA1 area with structure disrupting, and it would get worse with the development of disease course. HNYCF extract could improve the learning and memory ability of APP transgenic mice model, its mechanism might relate with improving ultrastructure of mitochondria in hippocampus, and increasing its quantity.
Geratology Center of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
Mingfang
M
Liu
Hao
H
Li
Jian'gang
J
Liu
Longtao
L
Liu
Jie
J
Guan
Linlin
L
Cai
Jia
J
Hu
Yun
Y
Wei
D000367:Age Factors; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000648:ultrastructure*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008516:Medicine, Chinese Traditional; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure*; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms
D004365:Drugs, Chinese Herbal