Staff Fellow — Division of Neurotoxicology

Jennifer Lynn Walters, Ph.D.
(870) 543-7121
NCTRResearch@fda.hhs.gov  

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 About  |  Publications 

Background

Dr. Walters has over 10 years of experience conducting research in neurotoxicology and pharmacology. She received a Ph.D. in behavioral pharmacology/psychology from Western Michigan University (WMU) and received a graduate certificate in regulatory science from the University of Arkansas for Medical Sciences. While at WMU, she acquired extensive experience using multiple techniques to screen drugs and other agents for therapeutic utility and adverse central nervous system effects. As a graduate student, she was awarded multiple teaching assistantships and travel awards. She was also awarded a graduate student research grant to support her dissertation research, which investigated the long-term effects of developmental and chronic exposures to the herbicide atrazine on neurobehavioral development in rodents. She then completed postdoctoral fellowships in the Division of Neurotoxicology at FDA’s National Center for Toxicological Research (NCTR) and in the Department of Integrative Physiology and Neuroscience at Washington State University (WSU). Her research at NCTR focused on understanding the neurotoxic effects of developmental exposures to volatile anesthetics in nonhuman animal models, while her research at WSU focused on elucidating the pharmacological, functional neuroanatomical, and cellular mechanisms underlying opioid- and cocaine-seeking behavior in rats.

While at NCTR she received extensive training in functional brain anatomy and histopathological and immunohistochemical techniques. Likewise, at WSU she acquired experience using advanced neuroscience techniques, including in-vivo optogenetics and sophisticated animal models of drug self-administration and relapse. She was also awarded grant funding from the State of Washington’s Alcohol and Drug Abuse Research Program to study treatments for heroin abuse and relapse in rodent models. After completion of her postdoctoral fellowship at WSU, Jennifer joined W.L. Gore and Associates as a study director where she collaborated with a team of research scientists, laboratory science specialists, veterinary surgeons, pathologists, and engineers to lead the execution of nonclinical cardiovascular device research studies. Through this experience, Dr. Walters became proficient at leading high-profile, fast-paced, GLP studies, and became familiar with an array of complex surgical techniques performed by veterinary research surgeons. With a desire to continue conducting developmental neurotoxicology/pharmacology research in high priority areas for the FDA, Jennifer rejoined NCTR’s Division of Neurotoxicology as a staff fellow in 2020.
 

Research Interests

Dr. Walters’s primary area of research is focused on identifying sensitive techniques to screen FDA agents of interest for developmental neurotoxicity in juvenile animal studies, with a specific focus on identifying long-term markers of neurotoxicity that correlate with acute developmental insults. To this end, she is currently using a rodent model of pediatric anesthesia-induced neurotoxicity to study the impact of developmental anesthesia exposure on synaptic architecture later in life. Neonatal anesthesia-induced neurotoxicity is a well-established phenomenon in nonclinical literature, with studies showing that general anesthesia during the peak of synaptogenesis results in robust and widespread neural cell death. Although there are inherent limitations to using the rodent model (e.g., small size of neonatal rodent presents challenges in monitoring physiological parameters during the anesthetic exposure), the breadth of data on anesthesia-induced neurotoxicity in rodents makes this model ideal for exploring sensitive markers of long-term neurotoxicity.

During early brain development, neurons are rapidly forming synaptic connections with each other, a process known as synaptogenesis. Any disruptions to this process during development could result in long-term alterations to the brain later in life. Indeed, abnormal synapse formation and function is believed to contribute to a variety of psychiatric conditions, including schizophrenia and autism spectrum disorders. Although anesthetic agents administered during the peak brain growth-spurt period in rodents have repeatedly been shown to result in widespread neural cell death, it is unclear whether this translates into long-term neurobehavioral deficits. Thus, Dr. Walters’s laboratory is focused on utilizing multiple techniques (e.g., histopathology, immunohistochemistry, viral tract tracing, molecular biology assays, multi-electrode array, and behavioral measures of cognition) to assess the effects of anesthesia-induced neural cell death on synapse physiology. If successful, this approach will allow for the detection of neurotoxicity weeks to months after the initial developmental insult.

In addition to her work with pediatric anesthetics, Dr. Walters is also interested in using rodent models to investigate the neural mechanisms underlying Neonatal Opioid Withdrawal Syndrome (NOWS) and to develop safe and effective treatment strategies for NOWS in newborn infants. NOWS is a phenomenon observed among infants exposed to opioids in utero and is a major public health problem, affecting ~6.5 out of 1000 hospital births in the United States. The pathophysiology of NOWS is not fully understood and effective treatment strategies are limited, with opioid replacement therapy (e.g., oral morphine, methadone, and buprenorphine) typically serving as the first line of treatment. Although necessary to prevent the adverse effects associated with opioid withdrawal, postnatal exposure to these drugs can also negatively impact neurobehavioral development. Thus, Dr. Walters is interested in developing a rodent model of NOWS to 1) investigate the neural mechanisms underlying this phenomenon, 2) understand the long-term neurobehavioral effects of gestational and neonatal opioid exposure, and 3) explore novel effective, yet safe, treatment strategies for NOWS.

Professional Societies/National and International Groups

Arkansas Chapter of the Society for Neuroscience
Member
2015 – 2018, Present

Developmental Neurotoxicology Society
Member
2015 – 2018

National Center for Toxicological Research Institute for Animal Care and Use Committee
Member
2020 – Present

Society for Neuroscience
Member
2015 – Present

Society of Quality Assurance
Member
2019 – 2020

South Central Chapter, Society of Toxicology
Member
2017 – 2018

Selected Publications

Basolateral Amygdala Corticotropin-Releasing Factor Receptor Type 1 Regulates Context-Cocaine Memory Strength During Reconsolidation in a Sex-Dependent Manner.
Ritchie J.L., Walters J.L., Galliou J.M.C., Christian R.J., Qi S., Savenkova M.I., Ibarra C.K., Grogan S.R., and Fuchs R.A.
Neuropharmacology. 2021, 200(1), 108819. doi.org/10.1016/j.neuropharm.2021.108819.

Regions of the Basal Ganglia and Primary Olfactory System are Most Sensitive to Neurodegeneration After Extended Anesthesia in the Perinatal Rat.
Burks S., Bowyer J., Walters J.L., and Talpos J.T.
Neurotoxicology and Teratology. 2020, 80, 106890. doi:10.1016/j.ntt.2020.106890.

Acetyl-L-carnitine Does Not Prevent Neurodegeneration in a Rodent Model of Prolonged Neonatal Anesthesia.
Walters J.L., Chelonis J.J., Fogle C.M., Ferguson S., Sarkar S., Talpos J.C., Paule M.G., and Talpos J.T.
Neurotoxicology and Teratology. 2020, 80, 106891 doi:10.1016/j.ntt.2020.106891.

Sevoflurane Exposure has Minimal Effect on Cognitive Function and Does Not Alter Microglial Activation in Adult Monkeys.
Walters J.L., Fogle C.M., Talpos J.C., Zhang X., and Paule M.G.
Neurotoxicology. 2019, 71, 159-167. doi: 10.1016/j.neuro.2018.12.008.

Developmental Neurotoxicity of General Anesthetics.
Walters J.L. and Paule M.G.
In: Slikker W., Paule M., and Wang C. (Eds.).
Handbook of Developmental Neurotoxicology (2nd ed.). 2018, 477-482. doi: 10.1016/B978-0-12-809405-1.00042-0.

Ontogeny of Monoamine Neurotransmitters.
Sarkar S., Imam S., and Walters J.
In: Slikker W., Paule M., and Wang C. (Eds.).
Handbook of Developmental Neurotoxicology (2nd ed.). 2018, 173-180. doi: 10.1016/B978-0-12-809405-1.00015-8.

Review of Preclinical Studies on Pediatric General Anesthesia-Induced Developmental Neurotoxicity.
Walters J.L. and Paule M.G.
Neurotoxicology and Teratology. 2017, 60, 2-23. doi:10.1016/j.ntt.2017.02.001.

Single and Repeated Exposures to the Volatile Anesthetic Isoflurane Do Not Impair Operant Performance in Aged Rats.
Walters J.L., Chelonis J.J., Fogle C.M., Orser B.A., and Paule M.G.
Neurotoxicology. 2016, 56, 159-169. doi:10.1016/j.neuro.2016.07.012.

The Use of Operant Tasks to Assess Cognition in Persons with Alzheimer’s Disease.
Walters J.L., Chelonis J.J., Gardner E.S., and Paule M.G.
American Journal of Alzheimer’s Disease. 2016, 3(1), 1-19. doi:10.7726/ajad.2016.1001.

The Effects of Gestational and Chronic Atrazine Exposure on Motor Behaviors and Striatal Dopamine in Male Sprague-Dawley Rats.
Walters J.L., Lansdell T.A., Lookingland K.J., and Baker L.E.
Toxicology and Applied Pharmacology. 2015, 289(2), 185-192. doi:10.1016/j.taap.2015.09.026.