Graduate Studies

 

First Advisor

James W. Checco

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Chemistry

Date of this Version

7-2024

Document Type

Dissertation

Citation

A dissertation presented to the faculty of the Graduate College of the University of Nebraska in partial fulfillment of requirements for the degree of Doctor of Philosophy

Major: Chemistry

Under the supervision of Professor James W. Checco

Lincoln, Nebraska, July 2024

Comments

Copyright 2024, Somayeh Mousavi. Used by permission

Abstract

Cell-cell signaling molecules known as neuropeptide and peptide hormones, distributed in both the central nervous system (CNS) and the peripheral nervous system (PNS), regulate a variety of physiological processes including body temperature, feeding, circadian rhythm, reproduction, energy homeostasis, and more. While a number of active neuropeptides structures with physiological functions have been discovered, advances in peptidomic mass spectrometry are enabling researchers to uncover novel, previously unknown, active neuropeptide structures with potential for bioactivities. Using liquid chromatography coupled with tandem mass spectrometry (MS/MS), it is possible to identify a wide range of neuropeptides in single experiments without preselecting specific peptides. Mass spectrometry is a cornerstone analytical technique in peptidomics, providing unparalleled sensitivity, specificity, and throughput for the study of peptides. It allows for the precise identification and characterization of these peptides, including their sequence, structure, and post-translational modifications such as phosphorylation, glycosylation, and acetylation. The ability to detect and analyze these modifications is particularly important, as these modifications can significantly impact peptide function and activity. Advanced mass spectrometry techniques, including (MS/MS) and high-resolution mass spectrometry, offer the resolution and accuracy needed to analyze complex peptide mixtures in biological samples. The integration of MS with bioinformatics tools facilitates the analysis of large datasets, enabling the identification of novel peptides and their functional roles. Overall, the application of mass spectrometry in peptidomics has revolutionized the field, offering comprehensive insights into the peptide landscape, uncovering novel biomarkers, and advancing our understanding of peptide-related diseases and therapeutic targets.

Our study offers valuable insights into the changes of endogenous peptides in the hypothalamus and pituitary during mammalian hibernation by using peptidomics analysis. These findings could inspire future applications of hibernation-like techniques for organ preservation and pave the way for deeper investigations into the molecular mechanisms underlying hibernation, which could uncover new therapeutic targets for the treatment of diseases like obesity and stroke. Also, our results demonstrate that acute anesthetic administration can be used in peptidomic experiments involving the brain tissues and pituitary without significantly affecting the measured peptide profiles.

Advisor: James W. Checco

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