# Effects of cholesterol perturbations on zebrafish nervous system development.

> **NIH NIH P20** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $160,686

## Abstract

PROJECT SUMMARY:
Neuronal sterol synthesis can be impacted by genetic mutations in cholesterol synthesis genes or by
psychopharmaceuticals that inhibit one of the sterol synthesis enzymes (shown in our ongoing studies).
Epidemiological studies and our ongoing studies have shown that the use of psychopharmaceuticals during
pregnancy is ubiquitous. Many commonly used medications have not been evaluated for safety during
pregnancy and the long-term consequences of fetal exposure remain unknown. Testing the effects of commonly
prescribed psychopharmaceuticals will provide insight into the role of cholesterol and fatty acids for the formation
and maturation of the zebrafish nervous system. We hypothesize that exposure to psychotropic pharmaceuticals
that inhibit cholesterol synthesis enzymes will alter neuronal cholesterol and acylcarnitine levels disrupt nervous
system development. Zebrafish larvae will be exposed to pharmaceuticals at several distinct developmental
stages and analyzed at 5 days post fertilization. LC-MS/MS will be used to measure sterol and oxysterol levels,
acylcarnitines, acetylated tubulin, as well as neuronal and glial specific markers. These studies will elucidate the
effects of commonly used psychotropic medications on sterol synthesis and acylcarnitine modification and
utilization as well as whole body and nervous system development and function in zebrafish larvae. Whole
zebrafish and brain immunohistochemistry will be used to visualize drug effects on brain development. In vivo
lateral line neurosensory cells and brain neural network electrical activity will be assessed using state-of-the -art
technologies available through the COBRE collaboration. Locomotor behavior of drug and control treated
zebrafish will be compared using ViewPoint Behavioral Technology. The outcome are threefold: 1. Our results
will identify drugs that should be used with extreme caution during pregnancy and provide a framework for future
preclinical testing of new therapeutic agents for sterol biosynthesis inhibition; 2. Our results will also provide
important information about the role of cholesterol homeostasis and acylcarnitine levels during nervous system
development and behavior; and 3. Our results will provide excellent training for graduate and undergraduate
research students in the fields of lipid biochemistry, sensory and central nervous system development,
physiology, and function by an experienced, dedicated working group of NE-INBRE and COBRE funded
scientists.

## Key facts

- **NIH application ID:** 10400500
- **Project number:** 3P20GM103427-20S1
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** PAUL L SORGEN
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $160,686
- **Award type:** 3
- **Project period:** 2001-09-30 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400500

## Citation

> US National Institutes of Health, RePORTER application 10400500, Effects of cholesterol perturbations on zebrafish nervous system development. (3P20GM103427-20S1). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10400500. Licensed CC0.

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