How does Diet influence Behavior and Neuroinflammation?

TY - ABST

T1 - How does Diet influence Behavior and Neuroinflammation?

AU - Jørgensen, Bettina Merete Pyndt

AU - Hansen, Julie Torpe

AU - Hansen, Axel Jacob Kornerup

AU - Sørensen, Dorte Bratbo

PY - 2011/11

Y1 - 2011/11

N2 - A high number of Non-responders in induced animal models of depression is a problem in research as it results in a high work load and a waste of animals. The aim of this project is to investigate the possible relationship between diet, gut microbiota (GM), low-grade inflammation in the brain, and behavior in order to generate knowledge enabling researchers to increase the number of responders when inducing these models using environmental modulation. The hypothesis is that a diet-induced change in GM composition can induce a cytokine mediated low-grade neuroinflammation, which is also observed in psychiatric diseases such as depression, thereby affecting the behavior. Furthermore the role of Brain Derived Neutrophic Factor (BDNF) in depressive behavior is investigated. 42 male BALB/c mice were divided in to three groups, and fed either a high-fat/low-sugar diet, a high-sugar/low-fat diet or a control starch-containing diet for 10 weeks. Blood samples were drawn after acclimatization, and fecal samples were taken at relevant time points during the study. Behavioral testing was performed before diet feeding using the Triple test and after the trial by the use of the Sucrose Preference test, the Burrowing test, the Triple test, the Forced Swim test and the Morris Water Maze test. At euthanization blood samples, fecal- and cecal samples and tissue samples were collected. Tissue samples included ileum, abdominal- and subcutaneous fat, hippocampus and prefrontal cortex. Cytokines in blood and brain tissue are still to be analyzed and so is the brain level of BDNF. Fecal- and cecal GM composition are currently being examined. Preliminary results shows that high-fat diet increased terminal weight (p<0.001) even though there was no difference between the groups before the diet feeding. This may lead to a systemic rise in proinflammatory cytokines, thereby inducing neuroinflammation. In the burrowing test the mice on control diet burrowed significantly more bedding out of the burrow (p=0.02). However, after the test it was noticed that the mice on sugar diet had been digging several places within the cage, indicating that their activity might be higher than the control mice, but their burrowing was more sporadic and not confined to only the burrow. This could indicate that the mice on sugar diet was hyper active and had trouble focusing on one activity. No difference in sucrose water preference was seen between the groups which were not in accordance with the hypothesis. In the Morris Water Maze mice fed a fatty diet showed a significant increased latency to reach the platform on day 3 compared to the two other groups. However, on day 4 this difference was diminished, indicating that a high fat diet leads to a less steep learning curve, which is in agreement with previous studies. It can be concluded that there were differences in behaviour between the three groups. Final analysis of all data from this study needs to be conducted before we can conclude more on this. There might be differences within groups, and the mice may cluster in sucrose preference in correlation to gut microbiota or neuroinflammation.

AB - A high number of Non-responders in induced animal models of depression is a problem in research as it results in a high work load and a waste of animals. The aim of this project is to investigate the possible relationship between diet, gut microbiota (GM), low-grade inflammation in the brain, and behavior in order to generate knowledge enabling researchers to increase the number of responders when inducing these models using environmental modulation. The hypothesis is that a diet-induced change in GM composition can induce a cytokine mediated low-grade neuroinflammation, which is also observed in psychiatric diseases such as depression, thereby affecting the behavior. Furthermore the role of Brain Derived Neutrophic Factor (BDNF) in depressive behavior is investigated. 42 male BALB/c mice were divided in to three groups, and fed either a high-fat/low-sugar diet, a high-sugar/low-fat diet or a control starch-containing diet for 10 weeks. Blood samples were drawn after acclimatization, and fecal samples were taken at relevant time points during the study. Behavioral testing was performed before diet feeding using the Triple test and after the trial by the use of the Sucrose Preference test, the Burrowing test, the Triple test, the Forced Swim test and the Morris Water Maze test. At euthanization blood samples, fecal- and cecal samples and tissue samples were collected. Tissue samples included ileum, abdominal- and subcutaneous fat, hippocampus and prefrontal cortex. Cytokines in blood and brain tissue are still to be analyzed and so is the brain level of BDNF. Fecal- and cecal GM composition are currently being examined. Preliminary results shows that high-fat diet increased terminal weight (p<0.001) even though there was no difference between the groups before the diet feeding. This may lead to a systemic rise in proinflammatory cytokines, thereby inducing neuroinflammation. In the burrowing test the mice on control diet burrowed significantly more bedding out of the burrow (p=0.02). However, after the test it was noticed that the mice on sugar diet had been digging several places within the cage, indicating that their activity might be higher than the control mice, but their burrowing was more sporadic and not confined to only the burrow. This could indicate that the mice on sugar diet was hyper active and had trouble focusing on one activity. No difference in sucrose water preference was seen between the groups which were not in accordance with the hypothesis. In the Morris Water Maze mice fed a fatty diet showed a significant increased latency to reach the platform on day 3 compared to the two other groups. However, on day 4 this difference was diminished, indicating that a high fat diet leads to a less steep learning curve, which is in agreement with previous studies. It can be concluded that there were differences in behaviour between the three groups. Final analysis of all data from this study needs to be conducted before we can conclude more on this. There might be differences within groups, and the mice may cluster in sucrose preference in correlation to gut microbiota or neuroinflammation.

KW - Det Sundhedsvidenskabelige Fakultet

KW - diet

KW - behavior

M3 - Konferenceabstrakt til konference

T2 - SHARE 2011

Y2 - 16 November 2011 through 16 November 2011

ER -