Kayla Lemons

Participant: PROMISE AGEP Research Symposium

Kayla Lemons
Department: Department of Biological Sciences
Institution: University of Maryland, Baltimore County (UMBC)

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PROMISE AGEP Research Symposium 2015

ABSTRACT

TRPM5-expressing microvillous cells are involved in modulation of olfactory function after irritant exposure

The main olfactory epithelium (MOE) in the nasal cavity detects inhaled odorants with high sensitivity. During inhalation, harmful microorganisms, pollutants, and irritants may also be introduced into the MOE. Mechanisms for detecting these substances in the MOE and regulating olfactory activity are poorly understood. We previously demonstrated that a set of microvillous cells (MCs) in the MOE expressing the transient receptor potential channel M5 (TRPM5) are responsive to harmful substances. Furthermore, these cells are capable of releasing acetylcholine (ACh), which alters intracellular calcium levels in neighboring cells. We hypothesize that cholinergic TRPM5-MCs play a role in the detection of foreign substances in the MOE and subsequently modulate olfactory activity. To investigate this, we continuously exposed Skn-1a knockout mice (Skn-1a-/-) which lack TRPM5-MCs in the MOE to odorous irritants for two weeks, and used behavioral assays to assess olfactory function. Under normal housing conditions, Skn-1a-/- and wild type mice perform similarly in finding buried food. After two weeks of continuous exposure, irritant-exposed Skn-1a-/- mice take longer to locate buried food than vehicle-exposed Skn-1a-/- mice, whereas the performance of wild type mice is unaltered by irritant exposure. Moreover, olfactory preference tests indicate that wild type mice avoid high concentration odorants to a greater extent after irritant exposure, while the tendency to avoid these stimuli is unchanged by irritant exposure in Skn-1a-/- mice. This preliminary data suggests that TRPM5-MCs contribute to the modulation of olfactory function in response to inhaled irritants.

PROMISE AGEP Research Symposium 2014

ABSTRACT

The Effects of Hydrocortisone on Tryptophan-2,3 dioxygenase and the Kynurenine Pathway

The Kynurenine pathway (KP) is a biochemical enzyme cascade responsible for metabolizing the essential amino acid Tryptophan. The hepatic enzyme Tryptophan-2,3 dioxygenase (TDO) is one of two enzymes that catalyze the initial breakdown of L-Tryptophan to N-Formylkynurenine in the first step of the pathway. It has previously been established in the literature that the steroid hormone Hydrocortisone induces TDO activity; however, the effects of Hydrocortisone on the KP as a whole have not yet been examined. Thus, given the role of TDO in the initial Tryptophan degradation step of the KP, we hypothesized that Hydrocortisone administration and the subsequent induction of TDO may cause significant changes in the levels of downstream KP metabolites. To test this hypothesis, Hydrocortisone was administered to 3 groups of mice which were sacrificed 1, 6, or 24 hours post-injection. High Performance Liquid Chromatography (HPLC) was then used to determine if there were any resulting differences in the levels of particular downstream KP metabolites in the liver, plasma and brain tissues of treated mice versus a saline-treated control group. This study has potentially great implications for the field of Neuropsychiatry, as several downstream KP metabolites are capable of influencing brain function by acting on various receptors and cell types in the brain. Given the known association between stress (which increases Hydrocortisone production) and the development of mental disorders, research into this topic could help clarify the proposed role of stress-related changes in the KP as a potential causative factor in the etiology of mental disorders.

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BIOGRAPHICAL SKETCH

Originally a native of Virginia, I earned my Bachelor’s degree in Biology and Cognitive Science from the University of Virginia in Charlottesville, Virginia. During my time as an undergraduate there, I served as a psychology research assistant in both the Virginia Affective Neuroscience (VAN) Lab and the Virginia Cognitive Aging Lab. I am currently a second year graduate student in the Neuroscience & Cognitive Science (NACS) doctoral program in the UMBC Biology Department.

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GENERAL SUMMARY OF GRADUATE RESEARCH

My research in Dr. Weihong Lin’s lab at UMBC focuses on understanding the olfactory system’s response to harmful foreign stimuli. Constant airflow from the external environment to the main olfactory epithelium (MOE) in the nasal cavity allows the olfactory system to detect airborne odor molecules with great sensitivity. However, potentially damaging foreign stimuli such as microorganisms, pollutants, and irritants can also enter the olfactory system in inhaled air. These substances threaten proper function of the olfactory system and other important structures such as the respiratory tract, lungs and brain. Although it is well-established that the MOE is capable of detecting and removing harmful substances in order to maintain its sensitivity, the mechanisms underlying this essential ability are poorly understood. My research aims to elucidate these mechanisms by investigating the potential role of microvillous cells (MCs) in the MOE which express the transient receptor potential channel M5 (TRPM5). We hypothesize that these cells detect harmful stimuli and modulate olfactory activity to preserve olfactory function. I am currently investigating whether these cells play a protective role by assessing olfactory ability in mice which lack TRPM5-MCs after continuous exposure to inhaled irritants. I hope that my research will ultimately contribute to the field by providing new insights about the mechanisms underlying olfactory protective responses.

SELECTED LIST OF PRESENTATIONS AND PUBLICATIONS

2014 University System of Maryland PROMISE AGEP Research Symposium. 02/2014
Oral Presentation: “The Effects of Hydrocortisone on Tryptophan-2,3 dioxygenase and the Kynurenine Pathway”.
UMBC 36th Annual Graduate Research Conference. 03/2014
Poster session winner: “The Effects of Irritant Exposure on the Olfactory Behavior of Skn-1a Knockout Mice”.
2014 University of Maryland Eastern Shore Regional Research symposium. 04/2014
2nd place Graduate oral presentation: “The Effects of Irritant Exposure on the Olfactory Behavior of Skn-1a Knockout Mice”.