The alteration of autophagy and apoptosis in the hippocampus of rats with natural aging-dependent cognitive deficits.
AIMS
The present study was aim to explore aging-dependent changes in hippocampal autophagy and apoptosis in a natural aging rat model from adult to old stages and to discover a suitable age for treating neurodegenerative diseases.


METHODS
Wistar rats at 5, 18 and 24months of age were used to mimic the adulthood, initial old, and old phases, respectively. The learning and cognitive ability of the rats was detected by the Morris water maze test. Morphological changes in the hippocampus were observed. Expressions of apoptosis and autophagy-related proteins were examined by Western blot.


RESULTS
The adult group (5months) exhibited high levels of autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II and cell survival, maintaining normal learning and cognitive function and integrated hippocampal morphology. The initial old group (18 months) presented a reduced number of neurons and cognitive deficits, and exhibited high levels of apoptosis related Bax/Bcl-2 ratio, Caspase-3 activation and autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II compared to the adult group. The old group (24 months) exhibited a high level of apoptosis related Bax/Bcl-2 ratio, Caspase-3 activation and a low level of autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II compared to its younger group, as well as significant neuronal death and cognitive deficits. The degree of autophagy was generally consistent with its negative regulator, the PI3K/Akt/mTOR axis, in all groups.


CONCLUSION
Our data suggest that cognitive deficits are first observed in the initial old stage. The levels of autophagy and apoptosis tend to be opposite in the adult and old phases. High levels of autophagy and apoptosis coexist in the initial old stage. Our study indicates that up-regulation of autophagy in the initial old phase to anti-cognitive deficits must be further evaluated.
['Yu|Yang|Y|', 'Feng|Linjing|L|', 'Li|Junnan|J|', 'Lan|Xiaoxin|X|', 'A|Lixiang|L|', 'Lv|Xiaoyan|X|', 'Zhang|Ming|M|', 'Chen|Li|L|']
D000375:Aging D000818:Animals D017209:Apoptosis D001343:Autophagy D003072:Cognition Disorders D015870:Gene Expression D006624:Hippocampus D008297:Male D018782:Maze Learning D023421:Models, Animal D017208:Rats, Wistar
Autophagy Apoptosis Aging mTOR Learning and memory decline