Alleviative Effect of Alpha-Lipoic Acid on Cognitive Impairment in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats
Background: The intricate relationship between type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) suggests that insulin is involved in modulating AD-related proteins. Alpha-lipoic acid (ALA) can improve insulin resistance (IR) in diabetic rats. However, the role of ALA in alleviating the c...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:4b35fe0043d342378a4257ead6f78e342021-11-12T06:30:49ZAlleviative Effect of Alpha-Lipoic Acid on Cognitive Impairment in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats1663-436510.3389/fnagi.2021.774477https://doaj.org/article/4b35fe0043d342378a4257ead6f78e342021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.774477/fullhttps://doaj.org/toc/1663-4365Background: The intricate relationship between type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) suggests that insulin is involved in modulating AD-related proteins. Alpha-lipoic acid (ALA) can improve insulin resistance (IR) in diabetic rats. However, the role of ALA in alleviating the cognitive decline of T2DM is not yet clear. This study examined the ameliorative effect of ALA on cognitive impairment, cerebral IR, and synaptic plasticity abnormalities in high-fat diet (HFD) plus streptozotocin (STZ) induced diabetic rats.Methods: The HFD/STZ-induced T2DM male Wistar rats were orally administered with ALA (50, 100, or 200 mg/kg BW) once a day for 13 weeks. Abilities of cognition were measured with a passive avoidance test and Morris water maze. Specimens of blood and brain were collected for biochemical analysis after the rats were sacrificed. Western blotting was used to determine protein expressions in the hippocampus and cortex in the insulin signaling pathways, long-term potentiation (LTP), and synaptic plasticity-related protein expressions.Results: Alpha-lipoic acid improved hyperinsulinemia and the higher levels of free fatty acids of the T2DM rats. Behavioral experiments showed that the administration of ALA improved cognitive impairment in HFD/STZ-induced T2DM rats. ALA ameliorated insulin-related pathway proteins [phosphoinositide 3-kinase (PI3K), phospho-protein kinase B (pAkt)/Akt, and insulin-degrading enzyme (IDE)] and the LTP pathway, as well as synaptic plasticity proteins (calmodulin-dependent protein kinase II, cyclic AMP response element-binding protein, and postsynaptic density protein-95) of the cerebral cortex or hippocampus in HFD/STZ-induced T2DM rats.Conclusion: Our findings suggested that ALA may ameliorate cognition impairment via alleviating cerebral IR improvement and cerebral synaptic plasticity in diabetic rats.Chih-Yuan KoChih-Yuan KoChih-Yuan KoChih-Yuan KoJian-Hua XuYangming Martin LoRong-Syuan TuJames Swi-Bea WuWen-Chung HuangSzu-Chuan ShenFrontiers Media S.A.articleα-lipoic acidAlzheimer’s diseasecerebral insulin signalinglong-term potentiationtype 2 diabetesNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021) |
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EN |
| topic |
α-lipoic acid Alzheimer’s disease cerebral insulin signaling long-term potentiation type 2 diabetes Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 |
| spellingShingle |
α-lipoic acid Alzheimer’s disease cerebral insulin signaling long-term potentiation type 2 diabetes Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Chih-Yuan Ko Chih-Yuan Ko Chih-Yuan Ko Chih-Yuan Ko Jian-Hua Xu Yangming Martin Lo Rong-Syuan Tu James Swi-Bea Wu Wen-Chung Huang Szu-Chuan Shen Alleviative Effect of Alpha-Lipoic Acid on Cognitive Impairment in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats |
| description |
Background: The intricate relationship between type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) suggests that insulin is involved in modulating AD-related proteins. Alpha-lipoic acid (ALA) can improve insulin resistance (IR) in diabetic rats. However, the role of ALA in alleviating the cognitive decline of T2DM is not yet clear. This study examined the ameliorative effect of ALA on cognitive impairment, cerebral IR, and synaptic plasticity abnormalities in high-fat diet (HFD) plus streptozotocin (STZ) induced diabetic rats.Methods: The HFD/STZ-induced T2DM male Wistar rats were orally administered with ALA (50, 100, or 200 mg/kg BW) once a day for 13 weeks. Abilities of cognition were measured with a passive avoidance test and Morris water maze. Specimens of blood and brain were collected for biochemical analysis after the rats were sacrificed. Western blotting was used to determine protein expressions in the hippocampus and cortex in the insulin signaling pathways, long-term potentiation (LTP), and synaptic plasticity-related protein expressions.Results: Alpha-lipoic acid improved hyperinsulinemia and the higher levels of free fatty acids of the T2DM rats. Behavioral experiments showed that the administration of ALA improved cognitive impairment in HFD/STZ-induced T2DM rats. ALA ameliorated insulin-related pathway proteins [phosphoinositide 3-kinase (PI3K), phospho-protein kinase B (pAkt)/Akt, and insulin-degrading enzyme (IDE)] and the LTP pathway, as well as synaptic plasticity proteins (calmodulin-dependent protein kinase II, cyclic AMP response element-binding protein, and postsynaptic density protein-95) of the cerebral cortex or hippocampus in HFD/STZ-induced T2DM rats.Conclusion: Our findings suggested that ALA may ameliorate cognition impairment via alleviating cerebral IR improvement and cerebral synaptic plasticity in diabetic rats. |
| format |
article |
| author |
Chih-Yuan Ko Chih-Yuan Ko Chih-Yuan Ko Chih-Yuan Ko Jian-Hua Xu Yangming Martin Lo Rong-Syuan Tu James Swi-Bea Wu Wen-Chung Huang Szu-Chuan Shen |
| author_facet |
Chih-Yuan Ko Chih-Yuan Ko Chih-Yuan Ko Chih-Yuan Ko Jian-Hua Xu Yangming Martin Lo Rong-Syuan Tu James Swi-Bea Wu Wen-Chung Huang Szu-Chuan Shen |
| author_sort |
Chih-Yuan Ko |
| title |
Alleviative Effect of Alpha-Lipoic Acid on Cognitive Impairment in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats |
| title_short |
Alleviative Effect of Alpha-Lipoic Acid on Cognitive Impairment in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats |
| title_full |
Alleviative Effect of Alpha-Lipoic Acid on Cognitive Impairment in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats |
| title_fullStr |
Alleviative Effect of Alpha-Lipoic Acid on Cognitive Impairment in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats |
| title_full_unstemmed |
Alleviative Effect of Alpha-Lipoic Acid on Cognitive Impairment in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats |
| title_sort |
alleviative effect of alpha-lipoic acid on cognitive impairment in high-fat diet and streptozotocin-induced type 2 diabetic rats |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/4b35fe0043d342378a4257ead6f78e34 |
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