Yang Yu1, Linjing Feng1, Junnan Li1, Xiaoxin Lan1, Lixiang A1, Xiaoyan Lv1, Ming Zhang2, Li Chen1. 1. Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, Jilin, China. 2. Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, Jilin, China. Electronic address: zhangming_00@126.com.
Abstract
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.
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.
Authors: Yahyah Aman; Tomas Schmauck-Medina; Malene Hansen; Richard I Morimoto; Anna Katharina Simon; Ivana Bjedov; Konstantinos Palikaras; Anne Simonsen; Terje Johansen; Nektarios Tavernarakis; David C Rubinsztein; Linda Partridge; Guido Kroemer; John Labbadia; Evandro F Fang Journal: Nat Aging Date: 2021-08-12
Authors: Ndidi-Ese Uzor; Diego Morales Scheihing; Gab Seok Kim; Jose Felix Moruno-Manchon; Liang Zhu; Caroline R Reynolds; Jessica M Stephenson; Aleah Holmes; Louise D McCullough; Andrey S Tsvetkov Journal: Mol Cell Neurosci Date: 2020-08-07 Impact factor: 4.314