Date of Award

2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Pharmacology

First Advisor

Yangguang Ou

Abstract

Short-chain fatty acids (SCFAs), one of the most abundant metabolites produced by gut bacteria, play a significant role in brain health and neurochemistry. Three of these SCFAs, acetate, propionate, and butyrate are the most predominant and have been shown to cross the blood-brain barrier (BBB) where they participate in the maintenance of neurovasculature, regulation of neurotransmitter levels, and energy expenditure. Although SCFAs serve as key molecules in gut-brain communication, imbalances in the composition of gut bacteria can cause shifts in SCFA levels which is seen in several neurological disorders, one of which is autism. Furthermore, evidence from mice models points to the concentration-dependent effect of individual SCFAs on autism phenotypes. A current gap in the field is the levels of SCFAs that cross the BBB during a healthy state and levels that cross the BBB during pathological states. Thus, to further understand their effect on disease pathogenesis, an electrochemical sensor that is sensitive and selective to SCFAs and a method that offers good spatiotemporal resolution to detect and measure these molecules needs to be developed. Here, we perform Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes for in vitro detection of SCFAs. We have strong evidence that suggest acetate, propionate, and butyrate are electroactive species and can be quantified using FSCV. We further optimized FSCV waveform parameters to improve the sensitivity of the electrode to our analytes of interest. Finally, we used butyrate analogs to derive a hypothesis regarding a potential faradaic mechanism behind SCFA electroactivity.

Language

en

Number of Pages

31 p.

Available for download on Saturday, April 12, 2025

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