Abstract
Background/aims:
To explore the effects of sulforaphane (SFN) on neuronal apoptosis in hippocampus and memory impairment in diabetic rats.
Methods:
Thirty male rats were randomly divided into normal control, diabetic model and SFN treatment groups (N = 10 in each group). Streptozotocin (STZ) was applied to establish diabetic model. Water Morris maze task was applied to test learning and memory. Tunel assaying was used to detect apoptosis in hippocampus. The expressions of Caspase-3 and myeloid cell leukemia 1(MCL-1) were detected by western blotting. Neurotrophic factor levels and AKT/GSK3β pathway were also detected.
Results:
Compared with normal control, learning and memory were apparently impaired, with up-regulation of Caspase-3 and down-regulation of MCL-1 in diabetic rats. Apoptotic neurons were also found in CA1 region after diabetic modeling. By contrast, SFN treatment prevented the memory impairment, decreased the apoptosis of hippocampal neurons. SFN also attenuated the abnormal expression of Caspase-3 and MCL-1 in diabetic model. Mechanically, SFN treatment reversed diabetic modeling-induced decrease of p-Akt, p-GSK3β, NGF and BDNF expressions.
Conclusion:
SFN could prevent the memory impairment and apoptosis of hippocampal neurons in diabetic rat. The possible mechanism was related to the regulation of neurotropic factors and Akt/GSK3β pathway.
© 2016 The Author(s) Published by S. Karger AG, Basel.
MeSH terms
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Animals
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Anticarcinogenic Agents / pharmacology
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Apoptosis / drug effects
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Brain-Derived Neurotrophic Factor / genetics
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Brain-Derived Neurotrophic Factor / metabolism
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Caspase 3 / genetics
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Caspase 3 / metabolism
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Cognitive Dysfunction / physiopathology
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Cognitive Dysfunction / prevention & control*
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Diabetes Mellitus, Experimental / chemically induced
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Diabetes Mellitus, Experimental / drug therapy*
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Diabetes Mellitus, Experimental / genetics
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Diabetes Mellitus, Experimental / physiopathology
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Drug Repositioning
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Gene Expression / drug effects
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Glycogen Synthase Kinase 3 beta / genetics
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Glycogen Synthase Kinase 3 beta / metabolism
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Hippocampus / drug effects
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Hippocampus / metabolism
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Hippocampus / pathology
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Hypoglycemic Agents / pharmacology*
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Isothiocyanates / pharmacology*
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Male
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Maze Learning / drug effects
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Memory / drug effects*
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Myeloid Cell Leukemia Sequence 1 Protein / genetics
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Myeloid Cell Leukemia Sequence 1 Protein / metabolism
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Nerve Growth Factor / genetics
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Nerve Growth Factor / metabolism
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Neurons / drug effects*
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Neurons / metabolism
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Neurons / pathology
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Rats
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Rats, Sprague-Dawley
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Streptozocin
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Sulfoxides
Substances
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Anticarcinogenic Agents
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Brain-Derived Neurotrophic Factor
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Hypoglycemic Agents
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Isothiocyanates
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Mcl1 protein, rat
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Myeloid Cell Leukemia Sequence 1 Protein
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Sulfoxides
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Streptozocin
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Nerve Growth Factor
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, rat
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Proto-Oncogene Proteins c-akt
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Casp3 protein, rat
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Caspase 3
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sulforaphane