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The density of sphingosine-1-phosphate receptors1-4 in the cerebral cortex of type-2-diabetes models

Erdogan, Hüseyin (2021) MOBN03 20202
Degree Projects in Molecular Biology
Abstract
Several, studies have shown the effect diet can have on brain function and metabolism, and it is widely acknowledged that rodents exposed to diets rich in fat develop brain dysfunction. The causes are related to fat-induced neuroinflammation, glucose neurotoxicity, and reduced insulin signaling, which affect brain structure and function, resulting in behavioral and cognitive changes. Recent studies have suggested that sphingosine-1-phosphate (S1P) plays a role during the development of diabetes, as well as growing protection against insulin resistance. In this study, we tested the hypothesis that type 2 diabetes (T2D) alters the levels of sphingosine-1-phosphate receptors 1-4 (S1PR1-4) in the cerebral cortex. We aimed at investigating the... (More)
Several, studies have shown the effect diet can have on brain function and metabolism, and it is widely acknowledged that rodents exposed to diets rich in fat develop brain dysfunction. The causes are related to fat-induced neuroinflammation, glucose neurotoxicity, and reduced insulin signaling, which affect brain structure and function, resulting in behavioral and cognitive changes. Recent studies have suggested that sphingosine-1-phosphate (S1P) plays a role during the development of diabetes, as well as growing protection against insulin resistance. In this study, we tested the hypothesis that type 2 diabetes (T2D) alters the levels of sphingosine-1-phosphate receptors 1-4 (S1PR1-4) in the cerebral cortex. We aimed at investigating the levels of the S1PR1-4 in different T2D rodent models to find a potential drug target for protection against cognitive decline related to T2D. Our study showed a decreased level of S1PR1-3 in T2D rodent models, these preliminary results indicate that stimulation of these receptors with specific agonists might aid synaptic function and improve memory in humans that have T2D. (Less)
Popular Abstract
A potential drug target to prevent cognitive decline and dysfunction caused by type-2-diabetes

Diabetes is not only one of the biggest diseases in the world, with 450 million cases but also one of the leading causes of death in the world around 70 thousand, and the most common type of diabetes is the type 2 variant (T2D), which is caused by insulin resistance. The amount of T2D cases seems to be steadily increasing with the years, probably because of the food we consume, in our diet which consist of more and more sugar and saturated fats causing insulin resistance and finally T2D. In some languages the word for diabetes is “sugar disease”.

The T2D has relations to the metabolism in our body, since insulin is a big factor in breaking... (More)
A potential drug target to prevent cognitive decline and dysfunction caused by type-2-diabetes

Diabetes is not only one of the biggest diseases in the world, with 450 million cases but also one of the leading causes of death in the world around 70 thousand, and the most common type of diabetes is the type 2 variant (T2D), which is caused by insulin resistance. The amount of T2D cases seems to be steadily increasing with the years, probably because of the food we consume, in our diet which consist of more and more sugar and saturated fats causing insulin resistance and finally T2D. In some languages the word for diabetes is “sugar disease”.

The T2D has relations to the metabolism in our body, since insulin is a big factor in breaking down sugar (glucose) and helping cells to store energy. Insulin does this by acting as a key that unlocks a door (the insulin receptor) so that sugar can enter the cell and be broken down into energy. However, when we have an excess amount of sugar available whenever we want, to open the door (the insulin receptor) one key is not enough, we need a lot more insulin for the cells to be able to absorb the glucose (it is called insulin resistance because a lot more insulin is needed, the cells become resistant to insulin).

Now there are many symptoms caused by T2D, and recently more studies have shown that brain function deteriorates causing worsen memory and brain impairment and that it might be related to the insulin pathway. Studies have also shown that another family of receptors namely the sphingosine-1-phosphate receptor 1-5 (S1PR1-5) play a big role in the development of T2D because of their relation to insulin pathway.

In this project we wanted to look at these receptors (S1PR1-5) as a potential drug target for preventing the cognitive decline that is caused by T2D. So various experiments were conducted like western blot, qPCR, and immunohistochemistry on brain tissue (cerebral cortex) from different T2D rodent models and compared with controls, I also did behavioural tests to look for difference in their cognitive abilities.

Our results showed us different density levels of S1PR1, S1PR2 and S1PR3 in the cerebral cortex of brain. these preliminary results indicate that stimulation of these receptors with specific agonist might aid synaptic function and improve memory in T2D.

Master’s Degree Project in Molecular Biology 60 Credits 2021

Department of Biology

Supervisor: PI Joao Duarte, Ph.D. Diabetes and Brain function, Department of Experimental Medical Science, BMC, Lund. (Less)
Please use this url to cite or link to this publication:
author
Erdogan, Hüseyin
supervisor
organization
course
MOBN03 20202
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9061444
date added to LUP
2021-07-09 10:31:30
date last changed
2021-07-09 10:31:30
@misc{9061444,
  abstract     = {{Several, studies have shown the effect diet can have on brain function and metabolism, and it is widely acknowledged that rodents exposed to diets rich in fat develop brain dysfunction. The causes are related to fat-induced neuroinflammation, glucose neurotoxicity, and reduced insulin signaling, which affect brain structure and function, resulting in behavioral and cognitive changes. Recent studies have suggested that sphingosine-1-phosphate (S1P) plays a role during the development of diabetes, as well as growing protection against insulin resistance. In this study, we tested the hypothesis that type 2 diabetes (T2D) alters the levels of sphingosine-1-phosphate receptors 1-4 (S1PR1-4) in the cerebral cortex. We aimed at investigating the levels of the S1PR1-4 in different T2D rodent models to find a potential drug target for protection against cognitive decline related to T2D. Our study showed a decreased level of S1PR1-3 in T2D rodent models, these preliminary results indicate that stimulation of these receptors with specific agonists might aid synaptic function and improve memory in humans that have T2D.}},
  author       = {{Erdogan, Hüseyin}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{The density of sphingosine-1-phosphate receptors1-4 in the cerebral cortex of type-2-diabetes models}},
  year         = {{2021}},
}