Forced running exercise mitigates radiation-induced cognitive deficits via regulated DNA hydroxymethylation

Aim: Roles of forced running exercise (FE) in remediation of neurogenesis inhibition and radiation-induced cognitive dysfunction were investigated in a whole-brain irradiation mice model via the regulation of DNA 5-hydroxymethylation modification (5 hmC) and its catalytic enzymes ten–eleven translocation (Tet) proteins. Materials & methods: Hippocampal neurogenesis and cognitive function, DNA 5 hmC level and Tet expression were determined in mice. Results: The expression of DNA 5 hmC and Tet2, brain-derived neurotrophic factor significantly decreased in hippocampus postradiation. FE mitigated radiation-induced neurogenesis deficits and cognitive dysfunction. Furthermore, FE increased 5 hmC and brain-derived neurotrophic factor expression. SC1, a Tet inhibitor, reversed partly such changes. Conclusion: Tet-mediated 5 hmC modification represents a kind of diagnostic biomarkers of radiation-induced cognitive dysfunction. Targeting Tet-related epigenetic modification may be a novel therapeutic strategy for radiation-induced brain injury.

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Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2013.12.031 ◽

2014 ◽

Vol 443 (2) ◽

pp. 646-651 ◽

Cited By ~ 59

Author(s):

Jian-feng Ji ◽

Sheng-jun Ji ◽

Rui Sun ◽

Kun Li ◽

Yuan Zhang ◽

...

Keyword(s):

Hippocampal Neurogenesis ◽

Neurocognitive Deficits ◽

Whole Brain Irradiation ◽

Whole Brain ◽

Running Exercise ◽

Brain Irradiation ◽

Forced Running

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Effects of Maternal Chewing on Prenatal Stress-Induced Cognitive Impairments in the Offspring via Multiple Molecular Pathways

International Journal of Molecular Sciences ◽

10.3390/ijms21165627 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5627

Author(s):

Qian Zhou ◽

Ayumi Suzuki ◽

Mitsuo Iinuma ◽

Ke-Yong Wang ◽

Kin-ya Kubo ◽

...

Keyword(s):

Prenatal Stress ◽

Neurotrophic Factor ◽

Cognitive Impairments ◽

Histone H3 ◽

Brain Derived Neurotrophic Factor ◽

Hippocampal Neurogenesis ◽

Morris Water Maze Test ◽

Molecular Pathways ◽

Mice Model ◽

Fk506 Binding Protein

We aimed to investigate the effects of maternal chewing on prenatal stress-induced cognitive impairments in the offspring and to explore the molecular pathways of maternal chewing in a mice model. Maternal chewing ameliorated spatial learning impairments in the offspring in a Morris water maze test. Immunohistochemistry and Western blot findings revealed that maternal chewing alleviated hippocampal neurogenesis impairment and increased the expression of hippocampal brain-derived neurotrophic factor in the offspring. In addition, maternal chewing increased the expression of glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase isozyme 2 (11β-HSD2) and decreased the expression of 11β-HSD1 in the placenta, thereby attenuating the increase of glucocorticoid in the offspring. Furthermore, maternal chewing increased the expression of 11β-HSD2, FK506-binding protein 51 (FKBP51) and FKBP52 and decreased the expression of 11β-HSD1, thereby increasing hippocampal nuclear GR level. In addition, maternal chewing attenuated the increase in expression of DNMT1 and DNMT3a and the decrease in expression of histone H3 methylation at lysine 4, 9, 27 and histone H3 acetylation at lysine 9 induced by prenatal stress in the offspring. Our findings suggest that maternal chewing could ameliorate prenatal stress-induced cognitive impairments in the offspring at least in part by protecting placenta barrier function, alleviating hippocampal nuclear GR transport impairment and increasing the hippocampal brain-derived neurotrophic factor (BDNF) level.

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