Environmental Enrichment and Metformin Improve Metabolic Functions, Hippocampal Neuron Survival, and Hippocampal-Dependent Memory in High-Fat/High-Sucrose Diet-Induced Type 2 Diabetic Rats
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals and Ethics Statement
2.2. Diets
2.3. Experimental Design
2.4. Environmental Enrichment (EE) Cages
2.5. T-Maze Tasks: Spontaneous Alternation and Rewarded Alternation
2.6. Spontaneous Alternation Task
2.7. Rewarded Alternation Task
2.8. Measurement of Anthropometric Parameters
2.9. Measurement of Fasting Blood Glucose (FBG)
2.10. Measurement of C-Peptide
2.11. Measurement of the Lipid Profile
2.12. Measurement of Oxidative Status
2.13. Measurement of Serum BDNF
2.14. Tissue Preparation
2.15. Histology
2.16. Image Morphometry
2.17. Morphometric Measurement of Adipose Tissue
2.18. Morphometric Measurement of Pancreatic Islets
2.19. Morphometric Measurement of Hippocampal Neurons
2.20. RNA Extraction
2.21. Analysis of Gene Expression by the Real-Time PCR
2.22. Statistical Analysis
3. Results
3.1. Effects of EE Exposure and Metformin Treatment on Fasting Blood Glucose (FBG), Serum C-Peptide, Histological Features, and Morphometric Measurement of Pancreatic Islets in HFS Diet-Induced T2D Rats
3.2. Effects of EE Exposure and Metformin Treatment on Serum Lipid Profile, Anthropometric Parameters, Histological Features, and Morphometric Measurement of Adipose Tissue in HFS Diet-Induced T2D Rats
3.3. Effects of EE Exposure and Metformin Treatment on Oxidative Status in HFS Diet-Induced T2D Rats
3.4. Effects of EE Exposure and Metformin Treatment on Spatial Learning and Memory Function, Serum BDNF, Histological Features, and Morphometric Measurement of Hippocampal Neurons in HFS Diet-Induced T2D Rats
3.5. Effects of EE Exposure and Metformin Treatment on Gene Expression in the Hippocampus of HFS Diet-Induced T2D Rats
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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RT2 qPCR Primer Assay Catalogue No. | Gene | NCBI Reference Sequence: | Official Name |
---|---|---|---|
PPR45425C | Akt1 | NM_033230 | v-akt murine thymoma viral oncogene homolog 1 |
PPR42749A | Atf4 | NM_024403 | activating transcription factor 4 |
PPR06577B | Bcl2 | NM_016993 | B-cell CLL/lymphoma 2 |
PPR45333A | Bdnf | NM_012513 | Brain-derived neurotrophic factor |
PPR43356B | Calm1 | NM_001007614 | calmodulin 1 |
PPR45142B | Camk2g | NM_133605 | calcium/calmodulin-dependent protein kinase II gamma |
PPR43063B | Grb2 | NM_030846 | growth factor receptor-bound protein 2 |
PPR06753B | Gria2 | NM_001083811 | glutamate receptor, ionotropic, AMPA 2 |
PPR06847D | Grin1 | NM_017010 | glutamate receptor, ionotropic, N-methyl D-aspartate 1 |
PPR44848A | Gsk3b | NM_032080 | glycogen synthase kinase 3 beta |
PPR44872B | Irs1 | NM_012969 | insulin receptor substrate 1 |
PPR47860F | Kras | NM_031515 | KRAS proto-oncogene, GTPase |
PPR43465A | Map2k1 | NM_031643 | mitogen-activated protein kinase 1 |
PPR48780A | Mapk1 | NM_053842 | mitogen-activated protein kinase 1 |
PPR45322B | Ntrk2 | NM_001163168 | neurotrophic tyrosine kinase, receptor, type 2 |
PPR59984F | Pik3ca | NM_133399 | phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha |
PPR45212A | Sh2b1 | NM_001048180 | SH2B adaptor protein 1 |
PPR06570C | Actb | NM_031144 | actin, beta |
PPR42247F | Hprt1 | NM_012583 | hypoxanthine phosphoribosyltransferase 1 |
PPR56649C | Pgk1 | NM_053291 | phosphoglycerate kinase 1 |
PPR47412A | Tbp | NM_001004198 | TATA box binding protein |
PPR63338A | GDC | Genomic DNA control | |
PPX63339A | PPC | PCR positive control | |
PPX63340A | RTC | Reverse transcription control |
Parameters/Group | C | D | DE | DM |
---|---|---|---|---|
FBG (mmol/L) | 5.90 ± 0.16 | 8.26 ± 0.48 * | 6.76 ± 0.10 † | 6.76 ± 0.34 † |
C-peptide (ng/mL) | 26.19 ± 13.65 | 94.30 ± 26.26 * | 53.03 ± 33.31 † | 40.35 ± 22.15 † |
Parameters/Group | C | D | DE | DM |
---|---|---|---|---|
TG (mmol/L) | 0.98 (0.97–1.13) | 2.54 (1.97–3.48) * | 1.58 (1.22–1.66) † | 1.69 (1.20–1.78) † |
TC (mmol/L) | 2.59 (2.59–2.60) | 3.25 (3.14–3.37) * | 2.63 (2.61–2.64) † | 2.69 (2.66–2.78) † |
HDL-C (mmol/L) | 1.98 (1.87–2.05) | 0.87 (0.68–1.24) * | 1.28 (1.24–1.34) | 1.30 (1.29–1.39) |
Initial Body Weight (g) | 240.7 ± 18.62 | 258.9 ± 37.52 | 271.5 ± 28.89 | 265.7 ± 43.99 |
Final Body Weight (g) | 385.9 ± 33.75 | 509.0 ± 48.85 * | 437.4 ± 21.80 † | 457.7 ± 59.02 |
PWG (%) | 60.3 ± 8.60 | 98.0 ± 13.12 * | 62.0 ± 9.63 † | 73.4 ± 13.91 † |
BMI (g/cm2) | 0.71 ± 0.04 | 0.87 ± 0.03 * | 0.74 ± 0.02 † | 0.78 ± 0.03 † |
AI (%) | 3.76 ± 0.75 | 8.91 ± 0.56 * | 4.87 ± 0.46 † | 5.51 ± 1.17 † |
Parameters/Group | C | D | DE | DM |
---|---|---|---|---|
FORT (mmol H2O2 Eq/L) | 2.03 ± 0.10 | 2.91 ± 0.18 * | 2.49 ± 0.03 † | 2.49 ± 0.09 † |
FORD (mmol/L Trolox Eq/L) | 1.43 ± 0.16 | 1.43 ± 0.15 | 1.64 ± 0.24 | 1.44 ± 0.17 |
Redox balance | 0.71 ± 0.05 | 0.49 ± 0.03 * | 0.66 ± 0.09 † | 0.58 ± 0.05 |
Parameters/Group | C | D | DE | DM |
---|---|---|---|---|
Spontaneous alternation (%) | 84.52 ± 6.234 | 67.86 ± 4.64 * | 85.12 ± 5.30 † | 85.71 ± 5.82 † |
Correct response (%) | 86.31 ± 5.75 | 67.26 ± 3.75 * | 80.36 ± 4.64 † | 79.76 ± 2.87 † |
Serum BDNF (ng/mL) | 14.45 ± 3.43 | 9.55 ± 1.67 * | 14.89 ± 1.00 † | 15.35 ± 2.27 † |
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Ismail, T.R.; Yap, C.G.; Naidu, R.; Pamidi, N. Environmental Enrichment and Metformin Improve Metabolic Functions, Hippocampal Neuron Survival, and Hippocampal-Dependent Memory in High-Fat/High-Sucrose Diet-Induced Type 2 Diabetic Rats. Biology 2023, 12, 480. https://doi.org/10.3390/biology12030480
Ismail TR, Yap CG, Naidu R, Pamidi N. Environmental Enrichment and Metformin Improve Metabolic Functions, Hippocampal Neuron Survival, and Hippocampal-Dependent Memory in High-Fat/High-Sucrose Diet-Induced Type 2 Diabetic Rats. Biology. 2023; 12(3):480. https://doi.org/10.3390/biology12030480
Chicago/Turabian StyleIsmail, Teh Rasyidah, Christina Gertrude Yap, Rakesh Naidu, and Narendra Pamidi. 2023. "Environmental Enrichment and Metformin Improve Metabolic Functions, Hippocampal Neuron Survival, and Hippocampal-Dependent Memory in High-Fat/High-Sucrose Diet-Induced Type 2 Diabetic Rats" Biology 12, no. 3: 480. https://doi.org/10.3390/biology12030480
APA StyleIsmail, T. R., Yap, C. G., Naidu, R., & Pamidi, N. (2023). Environmental Enrichment and Metformin Improve Metabolic Functions, Hippocampal Neuron Survival, and Hippocampal-Dependent Memory in High-Fat/High-Sucrose Diet-Induced Type 2 Diabetic Rats. Biology, 12(3), 480. https://doi.org/10.3390/biology12030480