Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Chemistry

Supervisor

Yeung, Ken

Abstract

Matrix-assisted laser/desorption ionization (MALDI) is the preferred method for mass spectrometry imaging (MSI) due to its high spatial resolution. Detecting small molecules like γ-aminobutyric acid (GABA) and glutamate, which are the main inhibitory and excitatory neurotransmitters respectively, proves challenging as their low masses conflict with background signals from most matrices.

This work optimizes zinc oxide nanoparticles (ZnO NP) as a matrix, focusing on GABA and Glutamate detection. Its absence of background signal makes ZnO suitable for small molecule detection. Its shortcomings, especially batch-to-batch variability, were mitigated through filtration and sonication before deposition, achieving high-resolution imaging of rat brain tissue sections.

To assess ZnO NP viability, MALDI MSI was employed to relatively quantify glutamate, glutamine, and GABA in brain tissue sections from adolescent rat brains exposed to Δ-9-tetrahydrocannabinol (Δ-9-THC) through edibles in the nucleus accumbens (NAc) subregions. ZnO NP consistently detected all, revealing a downregulation in each molecule in both subregions.

Summary for Lay Audience

Mass spectrometry imaging (MSI) has emerged as the leading technique in the field of molecular imaging, providing the composition and localization of various analytes within a wide range of biological tissues in a fast and practical manner. Matrix-assisted laser desorption/ionization (MALDI) is the most popular ionization technique for MSI experiments, using a matrix to ionize the analytes within the sample. MALDI enables the creation of molecular images for a multitude of chemical compounds, depending on the matrix employed.

Zinc oxide nanoparticles (ZnO NP) is a promising inorganic nanometric matrix capable of detecting a variety of small molecules and neurotransmitters. It can assess the abundance and localization of crucial neurotransmitters such as γ-aminobutyric acid (GABA) and glutamate in mouse and rat brain tissues. However, commercially available ZnO NP, like other nanometric matrices, is known to exhibit inherent variabilities, such as size variations across different batches and commercial providers. An optimization protocol was developed to minimize these variables, ensuring that the matrix consistently produces high-quality results.

Chronic exposure to Δ-9-tetrahydrocannabinol (THC), particularly during adolescence, has been shown to alter the total levels of GABA, Glutamate, and Glutamine in the prefrontal cortex region, especially in the Nucleus Accumbens (NAc), a region involved in reward processes, for both sexes. These neurochemical damages are reported to persist into adulthood. The optimized ZnO NP matrix was used in a comprehensive long-term study involving chronic THC edible administration to adolescent rats using Nutella as a vehicle. The MALDI studies reveal a decrease in total GABA, glutamine, and glutamate levels in the NAc core and NAc shell subregions of adolescent rat brains.

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