ApoE4 Knock-in Rat Project
Last fall we initiated a longitudinal study to characterize the behavior and physiology of an Alzheimer’s disease rat model. This model consists of a biallelic replacement of the rat ApoE gene with the human ApoE4 variant, a risk factor for Alzheimer’s disease in humans. This project consists of female and male unaffected and genetically altered Sprague Dawley rats and early indications are that female ApoE4 rats are more affected earlier than male ApoE4 rats on cognitive and affective tests. These initial findings were from the fall 2018 senior thesis of Lisa Blackmer-Raynolds ’19J and will be presented at the annual meeting of the Society for Neuroscience in Chicago in October. This fall, the rats are middle-aged and will be reexamined behaviorally by honors thesis student, Kaitlin McManus ’20.
Prenatal Choline Deficiency Projects
This year the lab will deviate from our usual focus on prenatal choline supplementation to focus instead on prenatal choline deficiency. We have ample evidence of the adult neuroprotective properties of supplemental choline levels in early life but many unanswered questions about the consequences of early life choline deficiency. Several students will be conducting projects on this topic: an honors thesis by Sam Gray ’20 will examine the vulnerability of prenatal choline deficient female and male rats to acute and chronic NMDA receptor antagonism; Andrea Swiderski ’20 will conduct a senior project focused on the ways in which prenatal choline deficiency affects a range of cognitive processes in female rats; and Martyna Czarnik ’21 along with lab RAs will conduct a pilot project as part of an independent study looking at whether prenatal choline deficiency leads to altered responses to stimulant drugs, such as cocaine and amphetamine.
DISC-1 (disrupted in schizophrenia) knockout Rats
As part of our ongoing efforts to develop and characterize valid models of human conditions and study the impacts of developmental factors, particularly nutriture, we are working with a rat with a genetic predisposition (biallelic functional deletion in the Disc1 gene) towards the development of schizophrenia-like symptoms. A major project in the lab is a longitudinal study tracking sensory gating deficits, marked by prepulse inhibition, and inhibitory interneurons, marked by parvalbumin immunohistochemistry, from preweaning to adulthood. This project was started by lab alum Stephanie Desrochers ’18 and its continuation is the senior thesis for Livia Stanger ’20. We are also excited about an RNA-seq study with female and male wild type and Disc1-KO rats. These data are currently being analyzed as part of the senior project of Aixin Yue ’20.
Mild Traumatic Brain Injury
We recently developed new methods to produce mild closed head injuries in rats and will continue our work using it to understand the influences of age, sex, and past injury history on behavioral and biological outcomes.