Mira Nakhle ‘20, Roxana Alvarez ‘20, Dr. Susan Masino, Dr. David Ruskin
3 thoughts on “Ketogenic Diet’s Impact on Social & Repetitive Behaviors in the BTBR Mouse Model of Autism”
Hi Mira,
I may have already asked you questions about this poster previously (I think this was presented in person a while back during a symposium?), but I’ll go ahead and ask again anyway:
Questions:
(1) Was this a repeated measures design? In other words, would the same mouse have been tested repeatedly, under each of the three diet conditions (pre-KD, during KD, and post-KD? I think this is the case, but just want to confirm.
(2) How do your findings directly compare to the analysis performed by Lizzie? Did she find a similar pattern of results when looking just at time spent in each chamber, during each phase?
(3) Clearly there are several potential reasons to explain why these BTBR mice fail to show the expected deficits in sociability. Imagine that the weakening of the phenotype with repeated breeding explanation is correct. What could you (or Prof. Ruskin) try, if you were committed to continuing studying ASD-like traits using BTBR mice?
So this frontal contact experimental paradigm is identical to Lizzie’s, and we were looking to replicate previous results specifically for the “reversal” group (mice that are fed CD, then KD, then CD again). Lizzie found significant increased sociability in the reversal group during KD (test 2) as compared to test 1, but the mice fell back to baseline when they returned to CD (test 3). In our replication, we did not observe a significant change in sociability from test 1 to tests 2 or 3. In terms of time spent in each chamber, we found these values to be similar across both Lizzie’s project and this project. In both cases, though, sociability measures gave results that were unexpected based on previous research by Prof. Masino and Prof. Ruskin.
One thing we have tried is to look at different measures of ASD behavior in the BTBR mice– for example, evaluating grooming as a proxy for stereotyped repetitive behaviors. In this experiment, we found that KD reduced grooming even after mice were reverted to CD, indicating lasting effects of KD on this behavior. I know that Prof. Masino and Prof. Ruskin have also used social transmission of food preference (STFP) tasks with BTBRs to look at communication and social learning, so that may be an option as well. Something else we talked about is just getting new BTBR mice to use for breeding. It is my understanding that phenotypic drift of inbred mice can be more sensitive to measures of anxious behavior (as opposed to, for example, ethanol preference), and in that case it may be a good idea to start fresh! Here is an interesting study I found that details this sort of variability between trials/labs:
Stability of inbred mouse strain differences in behavior and brain size between laboratories and across decades. Douglas Wahlsten, Alexander Bachmanov, Deborah A. Finn, and John C. Crabbe
PNAS October 31, 2006 103 (44) 16364-16369; https://doi.org/10.1073/pnas.0605342103
Thank you for your responses. Anecdotally, I have seen some evidence that animals with deficits in time spent in the chamber with the social target actually don’t show much of a deficit when frontal contact is examined. I would seem that frontal contact is not as sensitive a measure for social deficits, for whatever reason.
Hi Mira,
I may have already asked you questions about this poster previously (I think this was presented in person a while back during a symposium?), but I’ll go ahead and ask again anyway:
Questions:
(1) Was this a repeated measures design? In other words, would the same mouse have been tested repeatedly, under each of the three diet conditions (pre-KD, during KD, and post-KD? I think this is the case, but just want to confirm.
(2) How do your findings directly compare to the analysis performed by Lizzie? Did she find a similar pattern of results when looking just at time spent in each chamber, during each phase?
(3) Clearly there are several potential reasons to explain why these BTBR mice fail to show the expected deficits in sociability. Imagine that the weakening of the phenotype with repeated breeding explanation is correct. What could you (or Prof. Ruskin) try, if you were committed to continuing studying ASD-like traits using BTBR mice?
Hi Professor Martinez, thank you for your note!
Yes, this was a repeated measures design.
So this frontal contact experimental paradigm is identical to Lizzie’s, and we were looking to replicate previous results specifically for the “reversal” group (mice that are fed CD, then KD, then CD again). Lizzie found significant increased sociability in the reversal group during KD (test 2) as compared to test 1, but the mice fell back to baseline when they returned to CD (test 3). In our replication, we did not observe a significant change in sociability from test 1 to tests 2 or 3. In terms of time spent in each chamber, we found these values to be similar across both Lizzie’s project and this project. In both cases, though, sociability measures gave results that were unexpected based on previous research by Prof. Masino and Prof. Ruskin.
One thing we have tried is to look at different measures of ASD behavior in the BTBR mice– for example, evaluating grooming as a proxy for stereotyped repetitive behaviors. In this experiment, we found that KD reduced grooming even after mice were reverted to CD, indicating lasting effects of KD on this behavior. I know that Prof. Masino and Prof. Ruskin have also used social transmission of food preference (STFP) tasks with BTBRs to look at communication and social learning, so that may be an option as well. Something else we talked about is just getting new BTBR mice to use for breeding. It is my understanding that phenotypic drift of inbred mice can be more sensitive to measures of anxious behavior (as opposed to, for example, ethanol preference), and in that case it may be a good idea to start fresh! Here is an interesting study I found that details this sort of variability between trials/labs:
Stability of inbred mouse strain differences in behavior and brain size between laboratories and across decades. Douglas Wahlsten, Alexander Bachmanov, Deborah A. Finn, and John C. Crabbe
PNAS October 31, 2006 103 (44) 16364-16369; https://doi.org/10.1073/pnas.0605342103
Let me know if you have any other questions!
Hi Mira,
Thank you for your responses. Anecdotally, I have seen some evidence that animals with deficits in time spent in the chamber with the social target actually don’t show much of a deficit when frontal contact is examined. I would seem that frontal contact is not as sensitive a measure for social deficits, for whatever reason.
Best,
Prof. Martinez