The vibrant, diverse neuroscience community at Illinois is working to find solutions to some of today’s most pressing societal health challenges in fields including aging; learning, memory and plasticity; nutrition and cognition; neuroengineering; neuro-and socio-genomics; bioinformatics; and more. More than 300 faculty and staff on the Urbana-Champaign campus identify as researchers in the neuroscience space—regardless of their home department affiliation. These researchers are using leading-edge imaging tools, pioneering studies that progress from the lab to clinical applications with the goal of improving the health and lives of people everywhere.
Catherine Christian, PhD
Assistant Professor, Molecular and Integrative Physiology
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Professor Christian's research interests focus on areas of synaptic transmission, cellular excitability, neuromodulation, and circuit plasticity in the contexts of neuroendocrinology and epilepsy. She is specifically interested in temporal lobe epilepsy, which is most common among adults and how it relates to higher rates of reproductive endocrine disorders.
Explain your research in neuroscience; what are you investigating?
Both women and men with temporal lobe epilepsy, the most common form of epilepsy seen in adults, show higher rates of reproductive endocrine disorders in comparison with the general population. These disorders include polycystic ovary syndrome, menstrual cycle irregularities, and premature menopause in women, and semen abnormalities and low testosterone levels in men. Importantly, reproductive endocrine problems can reciprocally impact the severity of epilepsy seen and influence the choice and efficacy of anti-seizure treatments. My research is focused on identifying the changes in the brain linking epilepsy to reproductive endocrine disorders.
Notably, the areas of the brain in which the seizures are generated in temporal lobe epilepsy (hippocampus, cortex, and amygdala) are separate from that involved in the brain’s control of reproduction (hypothalamus). How do seizures in these other areas of the brain impact the hypothalamus, and what types of changes occur? To answer these questions, we are currently focusing on the gonadotropin-releasing hormone (GnRH) neurons of the hypothalamus, which form the main output of the brain controlling reproduction, and examining changes in their function induced in a mouse model of temporal lobe epilepsy.
How are you currently conducting your research?
We employ a model of temporal lobe epilepsy in which we inject a very small amount of a convulsant drug called kainate into the hippocampus of adult mice. Over the weeks and months following this injection, the mice develop seizures and pathology that are similar to what is often seen in human temporal lobe epilepsy. Once the mice have developed epilepsy, we can then prepare thin slices through the hypothalamus and keep the cells in the slices alive for several hours, which gives us time to target individual neurons and record their electrical output, examine their cellular electrical properties, and record incoming signals from other neurons (synaptic transmission). This technique is called “patch clamp electrophysiology.” Using these methods, we have recently discovered that GnRH neurons show dramatic changes in activity in epileptic mice. Intriguingly, the types of changes we see are different between males and females, and in female mice, are dramatically different depending on the stage of the reproductive cycle in which we are doing our measurements. We also integrate measurements of hormone levels, recordings of seizure activity in electroencephalography (EEG), and evaluation of brain pathology to examine changes in this mouse model at multiple levels.
How does being part of the broader Illinois research community support and enhance your work?
Illinois has been an ideal environment in which to embark on this project. There are major strengths in neurobiology, endocrinology and reproductive sciences on campus. For example, we have collaborated with Jodi Flaws in Comparative Biosciences to measure changes in circulating sex hormones (estradiol, progesterone, and testosterone) in our control and epileptic mice. We have also collaborated with Mark Nelson in my home department, Molecular and Integrative Physiology (MIP), to apply computational analysis to our recording data to determine changes in the patterns of GnRH neuron activity induced by epilepsy. Going forward, we will work with Lori Raetzman, an expert in the pituitary gland (the main target of the GnRH hormone) who is also in MIP, to examine whether gene expression in the pituitary is changed with epilepsy.
In other projects, we are collaborating with Justin Rhodes in Psychology to conduct experiments on learning and memory behaviors in mice, and with Stephen Boppart in Engineering to use state-of-the-art imaging developed by his lab to examine interactions between neurons and astrocytes, two major cell types in the brain.
What led to your interest in this particular area of research?
In my PhD dissertation research at Virginia, I learned the techniques of patch clamp electrophysiology and investigated the mechanisms by which the brain controls the timing of ovulation. That work introduced me to the study of GnRH neurons and their physiological properties. I then did a postdoctoral fellowship in the Epilepsy Research Laboratories at Stanford. While I was learning more about epilepsy, I read papers from the clinical literature that described the increased incidence of reproductive endocrine disorders in people with epilepsy, as well as the challenges involved in treating women with epilepsy due to the complex changes in hormonal feedback effects on the brain that occur in women. Although some basic research had been done examining reproductive endocrine co-morbidities in rodent models of epilepsy, I saw that bringing the knowledge and skill set I had developed in graduate school to the epilepsy field would enable me to tackle this problem in a new way. When I started my independent lab at Illinois four years ago, I immediately got to work on setting up this area of research.
In what ways to you envision your work improving society or reaching people?
This work will provide new clues and targets in the treatment of reproductive co-morbidities that are commonly seen in epilepsy, which will aid in not only treating the endocrine disorders, but will also help in treating the underlying epilepsy as well. Moreover, this knowledge will have broader benefits in enabling a greater understanding of the complex interplay between endocrine systems and brain function, which has implications for understanding changes associated with puberty, menopause, stress, and mood disorders.
