Dapagliflozin diminishes memory and cognition impairment in Streptozotocin induced diabetes through its effect on Wnt/β-Catenin and CREB pathway
Diabetic neuropathy is a chronic condition that affects a significant number of individuals with diabetes. Streptozotocin injection intraperitoneally to rodents produces pancreatic islet β-cell destruction causing hyperglycemia, which affect the brain leading to memory and cognition impairment. Dapa...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923022000260 |
| _version_ | 1797367836694282240 |
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| author | Hala El-Safty Ashraf Ismail Rania M. Abdelsalam Ayman E. El-Sahar Muhammed A. Saad |
| author_facet | Hala El-Safty Ashraf Ismail Rania M. Abdelsalam Ayman E. El-Sahar Muhammed A. Saad |
| author_sort | Hala El-Safty |
| collection | DOAJ |
| description | Diabetic neuropathy is a chronic condition that affects a significant number of individuals with diabetes. Streptozotocin injection intraperitoneally to rodents produces pancreatic islet β-cell destruction causing hyperglycemia, which affect the brain leading to memory and cognition impairment. Dapagliflozin may be able to reverse beta-cell injury and alleviate this impairment. This effect may be via neuroprotective effect or possible involvement of the antioxidant, and anti-apoptotic properties. Forty rats were divided into four groups as follows: The normal control group, STZ-induced diabetes group, STZ-induced diabetic rats followed by treatment with oral dapagliflozin group and normal rats treated with oral dapagliflozin. Behavioral tests (Object location memory task and Morris water maze) were performed. Serum biomarkers (blood glucose and insulin) were measured and then the homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. In the hippocampus the followings were determined; calmodulin, ca-calmodulin kinase Ⅳ (CaMKIV), protein kinase A (PKA) and cAMP-responsive element-binding protein to determine the transcription factor CREB and its signaling pathway also Wnt signaling pathway and related parameters (WnT, B-catenin, lymphoid enhancer binding factor LEF, glycogen synthase kinase 3β). Moreover, nuclear receptor-related protein-1, acetylcholine and its hydrolyzing enzyme acetylcholine esterase, oxidative stress parameter malondialdehyde (MDA) and apoptotic parameter caspase-3 were determined. STZ was able to cause destruction to pancreatic β-cells which was reflected on glucose levels causing diabetes. Diabetic neuropathy was clear in the rats performing the behavioral tests. Memory and cognition parameters in the hippocampus were negatively affected. Oxidative stress and apoptotic parameter were elevated while the electrical activity was declined. Dapagliflozin was able to reverse the previously mentioned parameters and behavior. Thus, to say dapagliflozin significantly showed neuroprotective action along with antioxidant, and anti-apoptotic properties. |
| first_indexed | 2024-03-08T17:22:49Z |
| format | Article |
| id | doaj.art-8b62c5088fb040a2a2008f489299a00f |
| institution | Directory Open Access Journal |
| issn | 1873-2747 |
| language | English |
| last_indexed | 2024-03-08T17:22:49Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj.art-8b62c5088fb040a2a2008f489299a00f2024-01-03T04:11:12ZengElsevierBrain Research Bulletin1873-27472022-04-01181109120Dapagliflozin diminishes memory and cognition impairment in Streptozotocin induced diabetes through its effect on Wnt/β-Catenin and CREB pathwayHala El-Safty0Ashraf Ismail1Rania M. Abdelsalam2Ayman E. El-Sahar3Muhammed A. Saad4National Institute of Diabetes and Endocrinology, Cairo, Egypt; Corresponding author.Research and Training Center, National Institute of Diabetes and Endocrinology, Cairo, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt; School of Pharmacy, Newgiza University, Cairo, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt; School of Pharmacy, Newgiza University, Cairo, EgyptDiabetic neuropathy is a chronic condition that affects a significant number of individuals with diabetes. Streptozotocin injection intraperitoneally to rodents produces pancreatic islet β-cell destruction causing hyperglycemia, which affect the brain leading to memory and cognition impairment. Dapagliflozin may be able to reverse beta-cell injury and alleviate this impairment. This effect may be via neuroprotective effect or possible involvement of the antioxidant, and anti-apoptotic properties. Forty rats were divided into four groups as follows: The normal control group, STZ-induced diabetes group, STZ-induced diabetic rats followed by treatment with oral dapagliflozin group and normal rats treated with oral dapagliflozin. Behavioral tests (Object location memory task and Morris water maze) were performed. Serum biomarkers (blood glucose and insulin) were measured and then the homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. In the hippocampus the followings were determined; calmodulin, ca-calmodulin kinase Ⅳ (CaMKIV), protein kinase A (PKA) and cAMP-responsive element-binding protein to determine the transcription factor CREB and its signaling pathway also Wnt signaling pathway and related parameters (WnT, B-catenin, lymphoid enhancer binding factor LEF, glycogen synthase kinase 3β). Moreover, nuclear receptor-related protein-1, acetylcholine and its hydrolyzing enzyme acetylcholine esterase, oxidative stress parameter malondialdehyde (MDA) and apoptotic parameter caspase-3 were determined. STZ was able to cause destruction to pancreatic β-cells which was reflected on glucose levels causing diabetes. Diabetic neuropathy was clear in the rats performing the behavioral tests. Memory and cognition parameters in the hippocampus were negatively affected. Oxidative stress and apoptotic parameter were elevated while the electrical activity was declined. Dapagliflozin was able to reverse the previously mentioned parameters and behavior. Thus, to say dapagliflozin significantly showed neuroprotective action along with antioxidant, and anti-apoptotic properties.http://www.sciencedirect.com/science/article/pii/S0361923022000260Diabetic neuropathyMemory and cognitionDapagliflozinWnt/β-cateninCREB |
| spellingShingle | Hala El-Safty Ashraf Ismail Rania M. Abdelsalam Ayman E. El-Sahar Muhammed A. Saad Dapagliflozin diminishes memory and cognition impairment in Streptozotocin induced diabetes through its effect on Wnt/β-Catenin and CREB pathway Brain Research Bulletin Diabetic neuropathy Memory and cognition Dapagliflozin Wnt/β-catenin CREB |
| title | Dapagliflozin diminishes memory and cognition impairment in Streptozotocin induced diabetes through its effect on Wnt/β-Catenin and CREB pathway |
| title_full | Dapagliflozin diminishes memory and cognition impairment in Streptozotocin induced diabetes through its effect on Wnt/β-Catenin and CREB pathway |
| title_fullStr | Dapagliflozin diminishes memory and cognition impairment in Streptozotocin induced diabetes through its effect on Wnt/β-Catenin and CREB pathway |
| title_full_unstemmed | Dapagliflozin diminishes memory and cognition impairment in Streptozotocin induced diabetes through its effect on Wnt/β-Catenin and CREB pathway |
| title_short | Dapagliflozin diminishes memory and cognition impairment in Streptozotocin induced diabetes through its effect on Wnt/β-Catenin and CREB pathway |
| title_sort | dapagliflozin diminishes memory and cognition impairment in streptozotocin induced diabetes through its effect on wnt β catenin and creb pathway |
| topic | Diabetic neuropathy Memory and cognition Dapagliflozin Wnt/β-catenin CREB |
| url | http://www.sciencedirect.com/science/article/pii/S0361923022000260 |
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