Effects of a Ketogenic Diet on Prefrontal Cortical and Hippocampal Metabolic and Synapse-Related Proteins

Meagan Hoppe

Authors:  Meagan Hoppe, Abbi Hernandez, Caesar Hernandez, Keila Campos, Joe McQuail, Sara Burke

Faculty Mentor:   Sara Burke

College:  College of Medicine


With advancing age comes declining cognitive function. The potential to reverse these changes with dietary intervention holds promise for improving the quality of life of millions facing age-related cognitive decline. The prefrontal cortex (PFC) and hippocampus (HPC) are critical for supporting higher cognitive function, and both experience age-related decline in distinct ways. Previously, we investigated the ketogenic diet (KD) as a means for ameliorating declining cognitive function. However, the mechanism(s) of efficacy remain largely unknown. Therefore, this study investigated whether a KD alters synapse-related protein composition within the HPC of young and aged rats. Western blotting was used to quantify 10 synaptic proteins in the HPC synaptosome. Although this dietary regimen results improved cognitive outcomes, no protein levels were significantly altered by the KD. Additionally, Western blotting was used to compare membrane and cytosolic levels of the glucose transporter GLUT4, which is mobilized in response to insulin. Interestingly, young rats had differential expression of GLUT4 across brain regions. Furthermore, while aged rats had significantly altered GLUT4 mobilization relative to young in the PFC, this was ameliorated in aged KD-fed rats. Together, these data suggest KDs work through restoration of metabolism-related impairments rather than through synapse-related protein expression within the HPC.

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7 Responses
  1. Alex Angerhofer

    Hi Meagan, It looks like you did a lot of work and get interesting results. I am wondering how comparable rats are to humans in terms of the metabolism of their neurons. In other words I am wondering how well your research translates to humans.

    1. Meagan Hoppe

      That’s a very good question! Rats are excellent models of the human nervous system and share many similarities that allow for translation to humans. Notably, they age very similarly and experience similar deficits both behaviorally and metabolically. For example, aged humans tend to have a greater risk for metabolic disorders such has insulin insensitivity, and in our studies we’ve tested our rats’ levels of insulin with age and found that aged rats also experience significant insulin insensitivity. Just like in humans, rats utilize GLUT3 in neurons constitutively for transporting glucose and mobilize GLUT4 to transport glucose in an insulin-dependent manner. We also regularly test our control and ketogenic diet-fed rats for levels of glucose and the ketone body beta hydroxybutyrate, and these data show that rats on a KD can enter levels of ketosis comparable to humans through the same metabolic pathways.

  2. To follow-up on your hypothesis of a change in metabolism, do you think evaluating the metabolome in different brain areas of each of the 4 groups would be helpful?

    1. Meagan Hoppe

      You bring up an interesting idea! I’m not extremely familiar with the field of metabolomics, but from the basics I do know that does seem like an interesting direction to move forward with!