Anna Wadhwa

School: The New Jersey Institute of Technology

Major: Biochemistry

DOI: https://doi.org/10.21985/n2-zxxn-te44

Biography:

Anna is a senior at the New Jersey Institute of Technology, majoring in biochemistry with minors in philosophy and mathematical biology. She has been part of Dr. Steven Levison’s neurobiology lab at the Rutgers New Jersey Medical School for over a year, studying neurodevelopmental disorders in mice such as autism spectrum disorder (ASD). Anna is also involved in organizing NJIT’s first elementary STEM competition and holds leadership positions in Delta Phi Epsilon and NJIT’s Panhellenic Council. After graduation, she hopes to pursue an MD-PhD focusing on bioastronautics and the advancement of human space exploration to investigate the effects of extreme space environments on astronaut physiology. Outside of academics, Anna enjoys reading, baking, and skateboarding.

Sex-Dependent Behavioral Changes in a Mouse Model of Autism Spectrum Disorder

Abstract

According to the CDC, the incidence of Autism Spectrum Disorders (ASD) in the US has been consistently increasing. Animal models for neurodevelopmental disorders such as ASD indicate that several factors contribute to disease severity including genetics, prenatal infections, and sex. However, most studies using animal models have focused only on males, assuming females are simply attenuated males. Therefore, we investigated the impact of sex on behaviors associated with ASD. We induced systemic inflammation by injecting recombinant interleukin-6 (IL-6) twice daily from postnatal days 3-6, at a dose of 75 ng per injection, which we previously showed doubled plasma levels of IL-6 and produced social behavior deficits in male mice. 

Transiently increasing IL-6 soon after birth elicited a small but significant increase in body temperature that persisted for the first 2 months of life and was more notable in males. The IL-6 injected males also had decreased daily food intake at 9 weeks of age; however, this did not cause any growth delay. To determine the phenotypic effects of briefly increased systemic IL-6, we analyzed behaviors classically associated with ASD. At 10 weeks of age,both male and female mice were slower to find the goal box in the Barnes Maze of spatial memory, but this was due to increased freezing. Indeed, in female mice their memory of the task was significantly improved over PBS injected litter-mates. At 11 weeks, the IL-6 injected mice showed a trend, though nonsignificant, towards increased anxiety in the elevated plus maze and open field task, which was more prominent in females. At 17 weeks, both IL-6 injected sexes engaged in more self-grooming. Overall, our data support the conclusion that female mice respond differently to perinatal systemic inflammation and that their neuropsychiatric behavioral deficits are not simply an attenuated version of those seen in males.

What is your research topic, in a nutshell? 

We looked at the differences in autism presentation behaviors between males and females using a mouse model. 

How did you come to your research topic? 

My work (under Dr. Levison) was already focused on autism presentation behaviors but we had only been using male mice. In order to expand the focus of our work and investigate potential differences between males and females, we decided to test both and compare the two. 

Where do you see the future direction of this work leading (how might future researchers build on your work or what is left to discover in this field)?

Hopefully this can expand our understanding of sex-dependent characteristics in other neurodevelopmental disorders as well. We also want to further investigate the role of interleukin-6 in these behavioral deficits such as its signaling pathways in the brain, what proteins are involved in these changes such as synaptic markers or plasticity, what kind of electrophysiology differences we see, etc. 

Where are you heading to after graduation? 

I will be working as a post-bacc research fellow at the NIH investigating circadian rhythms and gene expression using a Drosophila model. After that, I hope to matriculate into an MD/PhD program studying bioastronautics and the advancement of human space exploration.