Dioxiodvanadium has been shown to successfully lower blood glucose concentrations in a diabetic rat model without toxicity to the heart, skeletal muscle, liver, kidney, and red blood cells. Therefore, this study aimed to investigate the effect of dioxidovanadium (V) on the hippocampus acutely and chronically, as well as the effects on diabetes-induced memory impairment in an STZ-induced diabetic animal model. To my family, thank you for making me the person I am today and supporting me throughout my education.
To Preshen, thank you for standing by me every step of the way. I thank you most deeply for helping me during the time I needed to complete my master's degree and most importantly, thank you for being my supervisor. Thank you for your constant support in my experimental work to my colleagues, Reveshna, Nombuso, Anelisiwe and Asipaphola.
Lindo and Malishca, thank you for sharing your knowledge and expertise with me. Endocrinology team, especially Palesa and Bongeka, thank you for always being available to guide and help me with my project.
LITERATURE REVIEW
Background
Glucose metabolism and function in the brain
The effects of diabetes on hippocampal metabolism
Pathological pathways of neurodegeneration in the hippocampus
- Diabetes and the generation of oxidative stress in the hippocampus
- The production of Amyloid Beta
- Hyper phosphorylation of Tau proteins
Implications of insulin therapy on the brain function
Alternative treatment for diabetes
- Transition metals and metal-based complexes
- Vanadium
- Vanadium complexes
Justification of the study
Aims
Objectives
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Administration of treatment
Behavioural studies
Tissue harvesting
Biochemical analysis
Blood glucose
Morris water maze task
The figure also includes graph B showing the probe test results calculated based on time spent in the target quadrant in all experimental groups (n=6) during the 7th day of the MWM task used to test for the speed of memory consolidation.
Hippocampal weights
Oxidative stress markers
The concentration of GPx1 in the DC group was significantly lower in concentration compared to the ND group θ (ND vs DC, p<0.05). It is also noteworthy that D-VAN was significantly higher than DC # (DC vs D-VAN, p<0.05) and INS group was significantly lower than D-VAN group α (D-VAN vs INS, p<0.05).
TNF-α
Amyloid beta (1-42)
This may be supported by our hippocampus weight results, which depict a smaller hippocampus in the diabetic groups compared to non-diabetic animals. It is important to note that the hippocampal weight in the brains of our ND-VAN group did not show a significant decrease in hippocampal weight compared to the untreated non-diabetic (ND) control group. According to our results, the concentration of MDA in the hippocampus of a diabetic model is significantly higher than a healthy animal, this confirms the strong connection between oxidative stress and diabetes.
In addition, the concentration of MDA in the non-diabetic vanadium-treated group was visibly lower, although not significantly different from the non-diabetic control, suggesting that vanadium (V) dioxide does not induce memory impairment through lipid peroxidation in the hippocampus. In our study, the induction of diabetes by STZ causes a significant decrease in the untreated diabetic control group (DC) compared to healthy animals in the non-diabetic control (ND). Research has shown that there is an increase in inflammation in the brain due to the cell damage mediated by oxidative stress caused by diabetes (52).
Increased destruction of neurons in the hippocampus will alter its function and may lead to memory impairment (54). Our study was only conducted for 5 weeks due to ethical constraints and therefore there was no detectable increase in TNF-α in the diabetes control compared to the non-diabetic control at this point in our study (55). In addition, studies have shown that increases in TNF-α in the hippocampus of diabetic patients are due to drastic changes in blood glucose concentration rather than a chronic hyperglycemic state (56).
This may be related to hypoglycemic drugs that can cause a cycle between hyperglycemia and hypoglycemia, which may explain the increase in TNF-α concentration in the hippocampus of the insulin-treated diabetic group. Another marker present in neurons in the hippocampus of patients with diabetes and considered a hallmark in the pathology of memory impairment is hyperphosphorylated tau (pTau). Despite the conflicting results for Aβ and pTau, there was a significant memory impairment in diabetic animals (DC) compared to non-diabetic animals (ND), as shown by our probe test result in the MWM task.
Therefore, we speculate that increased oxidative stress in diabetic animals led to increased production of acetylcholinesterase and thus affected memory consolidation (72). Furthermore, since dioxyvanadium significantly decreased MDA concentration and increased GPx1 concentration in the hippocampus of D-VAN, the animals' performance in the probe test may be due to diabetes rather than dioxydiovanadium(V). We can conclude by stating that dioxyvanadium significantly lowers blood glucose concentration in a diabetic animal model, while reducing oxidative stress in the hippocampus by reducing lipid peroxidation and increasing the antioxidant GPx1 in the brain of a hyperglycemic environment.
SYNTHESIS
Dioxidovanadium does not induce lipid peroxidation in hippocampal neurons in acute and chronic periods in the absence or presence of diabetes, suggesting that administration of dioxidovanadium is not toxic to the hippocampus. Please refer to the journal's authorship policy in the Editorial Policies and Ethical Considerations section for details on the appropriateness of author listing. The video/audio should make a specific point;. in particular, it must demonstrate the features described in the text of the manuscript.
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