Department of Cellular and Structural Biology

CSB Faculty


Brent J. Thompson, Ph.D.

Assistant Professor


Vanderbilt University, 2005




I joined the Department of Cellular and Structural Biology in 2009 after completing my postdoctoral training at Vanderbilt University where I was one of the first postdoctoral fellows accepted into the Vanderbilt Scientist Educator Program. As part of this program I was involved in teaching Gross Anatomy to the first year medical students. Currently I am a member of the American Association of Anatomists, where I have served on the Advisory Committee for Young Anatomists, and the Scientific Affairs Committee.


My postdoctoral research focused on the development and analysis of knock-in mice carrying polymorphisms in the gene encoding the serotonin transporter (SERT). Altered activity of this transporter has been proposed to be involved in numerous neuropsychiatric and developmental disorders including major depression, anxiety, obsessive compulsive disorder (OCD), and autism. SERT is also believed to be the primary target for selective serotonin-reuptake inhibitor (SSRI)-class antidepressants and some tricyclic antidepressants used to treat these disorders. Molecular, biochemical and behavioral phenotyping of mice carrying SERT polymorphisms has revealed traits including alterations in serotonin homeostasis, increased brain iron levels, loss of response to SSRI class antidepressants, and changes in depression and anxiety related behavioral tasks.


Research Interests:
In general the Thompson laboratory is interested in: regulation of the serotonin transporter (SERT), understanding how SSRI class antidepressants, such as Prozac, exert their clinical effects, the potential neurodevelopmental risks of prenatal SSRI exposure, development of the serotonergic nervous system, neurodevelopmental risks posed by altered SERT expression/activity and the impact altered serotonin signaling has on epigenetic regulation of gene expression.


Ongoing research projects in the Thompson laboratory


Project one: How do SSRI class antidepressants, such as Prozac, exert their clinical effects?
The Serotonin transporter (SERT) is thought to be the primary mechanism by which serotonin (5-HT) is cleared from the synaptic cleft to terminate serotonergic signaling. Dysregulation of SERT and the serotonergic nervous system has been implicated in numerous neuropsychiatric and developmental disorders including major depression, anxiety, obsessive compulsive disorder (OCD), and autism. Therefore it is not surprising that SERT is the primary target of selective serotonin reuptake inhibitors (SSRIs) used to treat these disorders. SSRIs are thought to act by inhibiting SERT mediated clearance of 5-HT from the synaptic cleft. However, this assumption may be incomplete, as it is well established that SSRIs have some affinity for other targets such the norepinephrine transporter and muscarinic, histaminergic and serotonergic receptors. Our understanding of the clinical effects of SSRIs is further confounded by the observation that SSRIs block serotonin uptake almost immediately, but the antidepressant effects can take weeks to manifest.


To better understand the mechanisms behind the therapeutic actions of SSRIs, we have created a line of knock-in mice (SERT I172M) carrying a single amino acid substitution that results in a loss of SERT sensitivity to multiple SSRIs, some tricyclic antidepressants and cocaine, while retaining normal serotonin transport (See fig 1). Ongoing studies are dissecting the biochemical and behavioral effects of SSRIs in an effort to define which effects are mediated by SERT blockade and which effects may be mediated by other targets of SSRIs. Additional studies are utilizing microarrays and quantitative RT-PCR to identify brain region specific alterations in gene expression following SSRI administration that may underlie the clinical effects of SSRIs. By utilizing the I172M SERT mice we will be able to distinguish SERT mediated changes in gene expression versus those mediated by other SSRI targets. For more information on the SERT I172M mice see the short presentation below.


Presented at the American Society for Pharmacology and Experimental Therapeutics (ASPET), April 2009:
Platform session entitled "The Serotonin Transporter: Not Just for Neurons Anymore"


Project two: Neurodevelopmental risks of early-life or prenatal exposure to SSRI class antidepressants.
An ongoing debate is "What is worse for a developing fetus, having a seriously depressed mother or being exposed in utero to antidepressants"? As SSRIs are considered generally safe with few serious side effects, approximately 3% of pregnant women continue to use SSRI class antidepressants throughout pregnancy to treat mood disorders.


Studies in animal models suggest that disruption of serotonergic signaling during neural development may alter the fine wiring of the fetal brain. For example, in rodent models, early life exposure to the SSRI fluoxetine (Prozac) results in an anxiety-like phenotype that persists into adulthood. Additionally, persistent changes in the expression of SERT and tryptophan hydroxylase have been found in rats exposed to SSRIs in the early postnatal period, which developmentally is roughly equivalent to the third trimester in humans. This has serious implications for the approximately ~3% of women who require SSRIs during pregnancy to treat mood disorders. Indeed, recent studies of newborn infants exposed to SSRIs in utero show that up to 30% of exposed newborns display a self-limiting neonatal behavior syndrome. Prenatal SSRI usage has also been associated with increased risk of premature birth, low birth weight, cardiovascular distress and septal heart defects. Although no studies have revealed a lasting impact on behavior or learning, most studies only follow the children for a few years. Therefore there is great need for well-controlled studies to examine both short and long term effects of these drugs on the developing brain.


We are currently examining the impact of early postnatal fluoxetine exposure on mouse behavior, brain development, neuronal gene expression and epigenetic regulation. These studies utilize behavioral testing paradigms such as the open field, elevated plus maze and social approach. The gene expression studies utilize microarrays, quantitative Real-Time PCR (qRT-PCR), genome wide methylation analysis by MBD-CAP-seq (methyl binding domain capture-sequencing) and pyrosequencing.


      Tornado map showing differential DNA methylation at or around the
      transcriptional start sites of selected genes following early-life exposure
      to fluoxetine (darker color indicates increased methylation).


Project three: Impact of maternal nutrition on development of the serotonergic nervous system. The Dutch Hongerwinter Winter and the Chinese Famine human epidemiology studies indicate an increased risk of schizophrenia and mood disorders in offspring whose mothers were subjected to under nutrition during pregnancy. Although under nutrition is a problem globally, its importance in the US is not generally appreciated despite the fact that ~ six million women of child bearing age in the US are subjected to food insecurity. Furthermore, conditions such as self-imposed dieting, suboptimal pregnancies, or poor placental function are essentially equivalent to under nutrition. It is hypothesized that these suboptimal conditions during pregnancy may result in "Fetal Programing" of life-long health. (Barker Hypothesis) The Center for Pregnancy and Newborn Research (CPNR) at UTHSCSA has developed an animal model of maternal nutrient restriction induced IUGR (intrauterine growth restriction) and generated an archive of brain samples from control and IUGR animals for further studies. As disruptions in serotonergic function have been implicated in the etiology of numerous neuropsychiatric disorders, we are utilizing this archive to study the impact IUGR has on development of the serotonergic nervous system. Methodologies utilized include immunohistochemistry, unbiased stereology, pharmacological assays (binding, receptor activation, 5-HT transport, etc.), qRT-PCR, methylation arrays and pyrosequencing.


Research Techniques:
Production and analysis of transgenic mice
Behavioral phenotyping of mice
Pharmacological studies of the serotonin transporter (SERT)
Gene expression (Microarray, Real Time quantitative RT-PCR)
Analysis of DNA methylation
Unbiased Stereology


Member of:


Veenstra-VanderWeele J, Muller CL, Iwamoto H, Sauer JE, Owens WA, Shah CR, Cohen J, Mannangatti P, Jessen T, Thompson BJ, Ye R, Kerr TM, Carneiro AM, Crawley JN, Sanders-Bush E, McMahon DG, Ramamoorthy S, Daws LC, Sutcliffe JS, Blakely RD. (2012) Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior. Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5469-74.


Thompson BJ, Jessen T, Henry LK, Field JR, Gamble KL, Gresch PJ, Carneiro AM, Horton RE, Chisnell PJ, Belova Y, McMahon DG, Daws LC, Blakely RD. (2011) Transgenic elimination of high-affinity antidepressant and cocaine sensitivity in the presynaptic serotonin transporter. Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3785-90.


Veenstra-Vanderweele J, Jessen TN, Thompson BJ, Carter M, Prasad HC, Steiner JA, Sutcliffe JS, Blakely RD. (2009) Modeling rare gene variation to gain insight into the oldest biomarker in autism: construction of the serotonin transporter Gly56Ala knock-in mouse. J Neurodev Disord. 2009 Jun;1(2):158-71.


Carneiro AM, Airey DC, Thompson B, Zhu CB, Lu L, Chesler EJ, Erikson KM, Blakely RD. (2009) Functional coding variation in recombinant inbred mouse lines reveals multiple serotonin transporter-associated phenotypes. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2047-52.


Thompson BJ, Washington MK, Kurre U, Singh M, Rula EY, Emeson RB. (2008) Protective roles of alpha-calcitonin and beta-calcitonin gene-related peptide in spontaneous and experimentally induced colitis. Dig Dis Sci. 2008 Jan;53(1):229-41.


Chastain CJ, Botschner M, Harrington GE, Thompson BJ, Mills SE, Sarath G, Chollet R. (2000) Further analysis of maize C(4) pyruvate,orthophosphate dikinase phosphorylation by its bifunctional regulatory protein using selective substitutions of the regulatory Thr-456 and catalytic His-458 residues. Arch Biochem Biophys. 2000 Mar 1;375(1):165-70.


Chastain CJ, Thompson BJ, and Chollet R. Maize recombinant C4-pyruvate, orthophosphate dikinase: Expression in Escherichia coli, partial purification, and characterization of the phosphorylatable protein. Photosynthesis Res. 1996; 49: 1 83-89.