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Ketogenic diet improves the spatial memory impairment caused by exposure to hypobaric hypoxia through increased acetylation of histones in rats
- Source :
- PLoS ONE, PLoS ONE, Vol 12, Iss 3, p e0174477 (2017)
- Publication Year :
- 2017
- Publisher :
- Public Library of Science (PLoS), 2017.
-
Abstract
- Exposure to hypobaric hypoxia causes neuron cell damage, resulting in impaired cognitive function. Effective interventions to antagonize hypobaric hypoxia-induced memory impairment are in urgent need. Ketogenic diet (KD) has been successfully used to treat drug-resistant epilepsy and improves cognitive behaviors in epilepsy patients and other pathophysiological animal models. In the present study, we aimed to explore the potential beneficial effects of a KD on memory impairment caused by hypobaric hypoxia and the underlying possible mechanisms. We showed that the KD recipe used was ketogenic and increased plasma levels of ketone bodies, especially β-hydroxybutyrate. The results of the behavior tests showed that the KD did not affect general locomotor activity but obviously promoted spatial learning. Moreover, the KD significantly improved the spatial memory impairment caused by hypobaric hypoxia (simulated altitude of 6000 m, 24 h). In addition, the improving-effect of KD was mimicked by intraperitoneal injection of BHB. The western blot and immunohistochemistry results showed that KD treatment not only increased the acetylated levels of histone H3 and histone H4 compared to that of the control group but also antagonized the decrease in the acetylated histone H3 and H4 when exposed to hypobaric hypoxia. Furthermore, KD-hypoxia treatment also promoted PKA/CREB activation and BDNF protein expression compared to the effects of hypoxia alone. These results demonstrated that KD is a promising strategy to improve spatial memory impairment caused by hypobaric hypoxia, in which increased modification of histone acetylation plays an important role.
- Subjects :
- Male
0301 basic medicine
Pulmonology
medicine.medical_treatment
lcsh:Medicine
Gene Expression
Ketone Bodies
Biochemistry
Hippocampus
Histones
Rats, Sprague-Dawley
Cognition
Learning and Memory
0302 clinical medicine
Medicine and Health Sciences
Post-Translational Modification
lcsh:Science
Hypoxia
Cyclic AMP Response Element-Binding Protein
Spatial Memory
Cognitive Impairment
Mammals
Multidisciplinary
biology
Cognitive Neurology
Chromosome Biology
Chemistry
Chromatin Modification
Chemical Reactions
Brain
Acetylation
Histone Modification
Animal Models
Lipids
Chromatin
Neurology
Experimental Organism Systems
Physical Sciences
Vertebrates
Ketone bodies
Epigenetics
Anatomy
medicine.symptom
Diet, Ketogenic
Research Article
Signal Transduction
medicine.medical_specialty
Cognitive Neuroscience
Histone Acetylation
Research and Analysis Methods
CREB
Rodents
Histone H4
03 medical and health sciences
Histone H3
Model Organisms
Memory
Internal medicine
DNA-binding proteins
Medical Hypoxia
Genetics
medicine
Animals
Memory impairment
Maze Learning
CA1 Region, Hippocampal
Cell damage
Memory Disorders
Brain-Derived Neurotrophic Factor
lcsh:R
Organisms
Biology and Life Sciences
Proteins
Cell Biology
Hypoxia (medical)
medicine.disease
Cyclic AMP-Dependent Protein Kinases
Rats
030104 developmental biology
Endocrinology
Amniotes
biology.protein
Cognitive Science
lcsh:Q
Protein Processing, Post-Translational
030217 neurology & neurosurgery
Neuroscience
Ketogenic diet
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....bd070e8c3d6bda71e8a5aae966511b82