scholarly journals Sedentary Life and Reduced Mastication Impair Spatial Learning and Memory and Differentially Affect Dentate Gyrus Astrocyte Subtypes in the Aged Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Fabíola de Carvalho Chaves de Siqueira Mendes ◽  
Luisa Taynah Vasconcelos Barbosa Paixão ◽  
Daniel Guerreiro Diniz ◽  
Daniel Clive Anthony ◽  
Dora Brites ◽  
...  

To explore the impact of reduced mastication and a sedentary lifestyle on spatial learning and memory in the aged mice, as well as on the morphology of astrocytes in the molecular layer of dentate gyrus (MolDG), different masticatory regimens were imposed. Control mice received a pellet-type hard diet, while the reduced masticatory activity group received a pellet diet followed by a powdered diet, and the masticatory rehabilitation group received a pellet diet, followed by powder diet and then a pellet again. To mimic sedentary or active lifestyles, mice were housed in an impoverished environment of standard cages or in an enriched environment. The Morris Water Maze (MWM) test showed that masticatory-deprived group, regardless of environment, was not able to learn and remember the hidden platform location, but masticatory rehabilitation combined with enriched environment recovered such disabilities. Microscopic three-dimensional reconstructions of 1,800 glial fibrillary acidic protein (GFAP)-immunolabeled astrocytes from the external third of the MolDG were generated using a stereological systematic and random sampling approach. Hierarchical cluster analysis allowed the characterization into two main groups of astrocytes with greater and lower morphological complexities, respectively, AST1 and AST2. When compared to compared to the hard diet group subjected to impoverished environment, deprived animals maintained in the same environment for 6 months showed remarkable shrinkage of astrocyte branches. However, the long-term environmental enrichment (18-month-old) applied to the deprived group reversed the shrinkage effect, with significant increase in the morphological complexity of AST1 and AST2, when in an impoverished or enriched environment. During housing under enriched environment, complexity of branches of AST1 and AST2 was reduced by the powder diet (pellet followed by powder regimes) in young but not in old mice, where it was reversed by pellet diet (pellet followed by powder and pellet regime again). The same was not true for mice housed under impoverished environment. Interestingly, we were unable to find any correlation between MWM data and astrocyte morphological changes. Our findings indicate that both young and aged mice subjected to environmental enrichment, and under normal or rehabilitated masticatory activity, preserve spatial learning and memory. Nonetheless, data suggest that an impoverished environment and reduced mastication synergize to aggravate age-related cognitive decline; however, the association with morphological diversity of AST1 and AST2 at the MolDG requires further investigation.

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Shi-Yu Sun ◽  
Xue-Yan Li ◽  
He-Hua Ge ◽  
Yu-Xin Zhang ◽  
Zhe-Zhe Zhang ◽  
...  

Increasing evidence indicates that exposure to inflammation during pregnancy intensifies the offspring’s cognitive impairment during aging, which might be correlated with changes in some synaptic plasticity-related proteins. In addition, an enriched environment (EE) can significantly exert a beneficial impact on cognition and synaptic plasticity. However, it is unclear whether gestational inflammation combined with postnatal EE affects the changes in cognition and synaptic plasticity-related proteins during aging. In this study, pregnant mice were intraperitoneally injected with lipopolysaccharides (LPS, 50 μg/kg) or normal saline at days 15–17 of pregnancy. At 21 days after delivery, some LPS-treated mice were randomly selected for EE treatment. At the age of 6 and 18 months, Morris water maze (MWM) and western blotting were, respectively, used to evaluate or measure the ability of spatial learning and memory and the levels of postsynaptic plasticity-related proteins in the hippocampus, including postsynaptic density protein 95 (PSD-95), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluA1 subunit, and Homer-1b/c. The results showed that 18-month-old control mice had worse spatial learning and memory and lower levels of these synaptic plasticity-related proteins (PSD-95, GluA1, and Homer-1b/c) than the 6-month-old controls. Gestational LPS exposure exacerbated these age-related changes of cognition and synaptic proteins, but EE could alleviate the treatment effect of LPS. In addition, the performance during learning and memory periods in the MWM correlated with the hippocampal levels of PSD-95, GluA1, and Homer-1b/c. Our results suggested that gestational inflammation accelerated age-related cognitive impairment and the decline of PSD-95, GluA1, and Homer-1b/c protein expression, and postpartum EE could alleviate these changes.


2021 ◽  
Vol 14 ◽  
Author(s):  
Zhan-Qiang Zhuang ◽  
Zhe-Zhe Zhang ◽  
Yue-Ming Zhang ◽  
He-Hua Ge ◽  
Shi-Yu Sun ◽  
...  

Studies have shown that gestational inflammation accelerates age-related memory impairment in mother mice. An enriched environment (EE) can improve age-related memory impairment, whereas mitochondrial dysfunction has been implicated in the pathogenesis of brain aging. However, it is unclear whether an EE can counteract the accelerated age-related memory impairment induced by gestational inflammation and whether this process is associated with the disruption of mitochondrial quality control (MQC) processes. In this study, CD-1 mice received daily intraperitoneal injections of lipopolysaccharide (LPS, 50 μg/kg) or normal saline (CON group) during gestational days 15–17 and were separated from their offspring at the end of normal lactation. The mothers that received LPS were divided into LPS group and LPS plus EE (LPS-E) treatment groups based on whether the mice were exposed to an EE until the end of the experiment. At 6 and 18 months of age, the Morris water maze test was used to evaluate spatial learning and memory abilities. Quantitative reverse transcription polymerase chain reaction and Western blot were used to measure the messenber RNA (mRNA) and protein levels of MQC-related genes in the hippocampus, respectively. The results showed that all the aged (18 months old) mice underwent a striking decline in spatial learning and memory performances and decreased mRNA/protein levels related to mitochondrial dynamics (Mfn1/Mfn2, OPA1, and Drp1), biogenesis (PGC-1α), and mitophagy (PINK1/parkin) in the hippocampi compared with the young (6 months old) mice. LPS treatment exacerbated the decline in age-related spatial learning and memory and enhanced the reduction in the mRNA and protein levels of MQC-related genes but increased the levels of PGC-1α in young mice. Exposure to an EE could alleviate the accelerated decline in age-related spatial learning and memory abilities and the accelerated changes in MQC-related mRNA or protein levels resulting from LPS treatment, especially in aged mice. In conclusion, long-term exposure to an EE can counteract the accelerated age-related spatial cognition impairment modulated by MQC in CD-1 mother mice that experience inflammation during pregnancy.


Lipids ◽  
2014 ◽  
Vol 49 (9) ◽  
pp. 855-869 ◽  
Author(s):  
Nursiati Mohamad Taridi ◽  
Nazirah Abd Rani ◽  
Azian Abd Latiff ◽  
Wan Zurinah Wan Ngah ◽  
Musalmah Mazlan

2020 ◽  
Author(s):  
Kazunori Sasaki ◽  
Noelia Geribaldi-Doldan ◽  
Qingqing Wu ◽  
Julie Davies ◽  
Francis G. Szele ◽  
...  

Abstract Background Much attention has recently focused on nutraceuticals which are widely used to promote health. In particular, nutraceuticals with minimal side effects have been developed for preventing or treating neurological diseases such as Alzheimer’s disease (AD). The present study was conducted to investigate the potential effect on neural development and function of the microalgae Aurantiochytrium sp. as a nutraceutical. Methods To test the neuroprotection of ethanol extract of Aurantiochytrium (EEA) and n-Hex layer of EEA (HEEA), amyloid-beta (Aβ)-stimulated SH-SY5Y cells was used for in vitro AD model. We then assessed the enhancement of neurogenesis of EEA and HEEA using murine ex vivo neurospheres. We also administered EEA or HEEA to SAMP8 mice, a non-transgenic strain with accelerated aging and Alzheimer’s-like memory loss for evaluation of spatial learning and memory using MWM test. Finally, we performed immunohistochemical analysis using mice brain fed with EEA for assessment of neurogenesis. Results Pre-treatment of SH-SY5Y cells with EEA or the squalene-rich fraction of EEA, n-Hex layer (HEEA), ameliorated Aβ-induced cytotoxicity. Interestingly, only EEA-treated cells showed a significant increase in cell metabolism and intracellular ATP production. Moreover, EEA treatment significantly increased the number of neurospheres, whilst HEEA treatment significantly increased the number of β-III-tubulin + young neurons and GFAP + astrocytes. SAMP8 mice were given 50 mg/kg EEA or HEEA orally for 30 days. Learning ability was assessed in the Morris water maze test. EEA and HEEA decreased escape latency time in SAMP8 mice, indicating improved memory. To detect activated stem cells and newborn neurons, we administered BrdU for 9 days and measured BrdU + cells in the dentate gyrus, a neurogenic stem cell niche of the hippocampus. In SAMP8 mice, EEA rapidly and significantly increased the number of BrdU + GFAP + stem cells as well as their progeny, BrdU + NeuN + mature neurons. Conclusions Our data in aggregate indicate that EEA and its constituents could be developed into a nutraceutical for promoting brain health and function against some age-related diseases including neurodegenerative desease, particularly AD.


Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6266
Author(s):  
Yang Zhou ◽  
Monica K. Chawla ◽  
Jose L. Rios-Monterrosa ◽  
Lingzhi Wang ◽  
Marc A. Zempare ◽  
...  

Brain G-protein coupled receptors have been hypothesized to be potential targets for maintaining or restoring cognitive function in normal aged individuals or in patients with neurodegenerative disease. A number of recent reports suggest that activation of melanocortin receptors (MCRs) in the brain can significantly improve cognitive functions of normal rodents and of different rodent models of the Alzheimer’s disease. However, the potential impact of normative aging on the expression of MCRs and their potential roles for modulating cognitive function remains to be elucidated. In the present study, we first investigated the expression of these receptors in six different brain regions of young (6 months) and aged (23 months) rats following assessment of their cognitive status. Correlation analysis was further performed to reveal potential contributions of MCR subtypes to spatial learning and memory. Our results revealed statistically significant correlations between the expression of several MCR subtypes in the frontal cortex/hypothalamus and the hippocampus regions and the rats’ performance in spatial learning and memory only in the aged rats. These findings support the hypothesis that aging has a direct impact on the expression and function of MCRs, establishing MCRs as potential drug targets to alleviate aging-induced decline of cognitive function.


2003 ◽  
Vol 25 (7) ◽  
pp. 455-474 ◽  
Author(s):  
J. Michael Wyss ◽  
Inga Kadish ◽  
Thomas van Groen

2012 ◽  
Vol 10 (1) ◽  
pp. 72 ◽  
Author(s):  
Jinwoo Lee ◽  
Sunmin Park ◽  
Ju-Young Lee ◽  
Yeong Keun Yeo ◽  
Jong Sang Kim ◽  
...  

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