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Zebrafish blue in an aquarium.

A researcher from the University of the Free State (UFS) hopes to make living with epilepsy and other diseases of the central nervous system (CNS) easier by using South African plants extracts which may have anti-epileptic properties and testing them on zebrafish larvae.

Prof Anke Wilhelm, Associate Professor and Divisional Head of Organic Chemistry in the UFS Department of Chemistry, focuses her research on the isolation of active GABAergic compounds (substances that affect the brain’s GABA system, which helps control nervous system activity) by using a test that measures the movement of zebrafish larvae.

Even though obtaining regulatory approval for use as a treatment for epilepsy is a long and complex process, Prof Wilhelm hopes to contribute to the better pain management of people suffering from epilepsy and diseases of the CNS through an affordable alternative drug with less side effects.

The tests are done in a zebrafish bioassay (an analytical method to determine the potency of a substance by its effect on living animals) housed at the UFS’ Chemistry Department.

Why zebrafish larvae?

Prof Wilhelm, who is a National Research Foundation Y2-rated synthetic organic chemist, says zebrafish share about 70% of their genes with humans, and about 84% of human genes known to be associated with diseases have a counterpart in zebrafish. This makes them a valuable model for studying human biology and disease.

“Zebrafish are powerful tools for modelling a wide range of CNS diseases, contributing significantly to the understanding of disease mechanisms and the development of potential treatments,” she says. “Mood disorders, anxiety, insomnia, and attention deficit hyperactivity disorder (ADHD) are all diseases which may be studied through this bioassay.”

She explains that the zebrafish larvae are studied seven days after fertilisation in their bioassay. The larvae are incubated with the specific plant extract at a certain (non-toxic) concentration for three hours. Pentylenetetrazol (PTZ), a GABAA receptor antagonist that has been extensively used in rodent models for acute seizure and anxiety, is then administered to induce concentration-dependent seizures in the zebrafish larvae.

“GABA receptor antagonists are drugs that inhibit the action of gamma-aminobutyric acid, the chief inhibitory neurotransmitter in the mammalian central nervous system,” Prof Wilhelm says. “A specialised infrared camera is then used to track the movement of the larvae inside a chamber. The data is then converted into a graph which shows the movement of each larva over 30 minutes.

“If lowering of movement is observed at a specific concentration it means that the plant extract may have the potential to be used as an epileptic drug, since it has the ability to counteract the induced seizure in the larvae. This bioassay is extremely useful in drug discovery and toxicity screening of plant extracts.”

Zebrafish embryos, she says, develop quickly, with major organs forming within 36 hours of fertilisation. This rapid development allows researchers to observe the effects of experiments in a short period. The maintenance of a zebrafish model is less costly and labour-intensive than using a rodent model. “The use of zebrafish larvae allows for high-throughput screening due to their small size and transparency, which facilitates observation of CNS-related effects. Their genetic and physiological similarities to humans make them a valuable model for early-stage drug discovery.”

Potential uses

The next step in the research, according to Prof Wilhelm, is to identify a single compound from a natural source which may have potential anti-epileptic activity while causing less side effects than current drugs on the market. Researchers would then investigate the possibility of synthesising such a compound on a large scale, to eliminate the use of a natural resource and promote sustainability.

“Many plant extracts which I have screened show a synergistic effect in the zebrafish bioassay, meaning that the extract or the combination of compounds shows potential, but the isolated compounds are inactive. Even if a plant extract shows promise in preclinical and early clinical studies, obtaining regulatory approval for use as a treatment for epilepsy is a long and complex process.

“This includes demonstrating consistent efficacy, safety, and quality in large-scale clinical trials. One of the major challenges in using plant extracts is the lack of standardisation. The concentration of active compounds in plant extracts can vary depending on factors like the plant's growing conditions, harvest time, and extraction methods. This variability makes it difficult to ensure consistent efficacy and safety, therefore this is a time-consuming process.”

Green chemistry

After being approached by Dr Glen Taylor, Senior Director of the UFS Directorate Research Development (DRD), in 2017, regarding funding for Noldus Daniovision equipment, Prof Wilhelm received training from Prof Matthias Hamburger of the University of Basel in Switzerland on how to use such equipment. The larval zebrafish locomotive bioassay was established at the UFS Chemistry Department during 2017 and 2018 and now provides a third-stream income for the department, in conjunction with the Department of Genetics, where the adult zebrafish are housed.

Prof Wilhelm’s other research interests include green chemistry, food sustainability, and recycling. She is looking into green extraction techniques using non-conventional extraction methods to recover valuable bioactive compounds from agricultural and food residues. “Techniques like ultrasound, microwave-assisted extraction, and the use of deep eutectic solvents are becoming popular for their efficiency and alignment with circular economy principles.”

News Archive

Teachers should deal with diversity in education - Prof. Francis
2010-10-08

At the occasion were, from the left: Prof. Jonathan Jansen, Rector and Vice-Chancellor of the University of the Free State (UFS); Prof. Francis; and Prof. Driekie Hay, Vice-Rector: Teaching and Learning at the UFS.
Photo: Jaco van der Merwe

Prof. Dennis Francis, the Dean of the Faculty of Education at the University of the Free State (UFS), recently delivered his inaugural lecture on Troubling Diversity in South African Education on the Main Campus in Bloemfontein.

He urged teachers to be open to what “diversity” might mean in a particular context and how diversity relates to either inclusion or exclusion.

“An approach that promotes the inclusion of all must be based on an understanding of how exclusion operates in ways that may have typical patterns of oppression, but differ in the specific ways that exclusion is expressed and becomes normalised in that context,” he said.

“The good teacher thus seeks to understand how these forms of exclusion may develop in the school’s context and respond through taking thoughtful action to challenge them. It may require creating a climate that enables the silent to speak and recognising that not all groups communicate in exactly the same ways.”

He said teachers also had to affirm the experiential base of learners and students. He said there was an assumption that students would be more effective practitioners if their own experience were validated and explored.

“It is crucial that the students’ own history is treated as valuable and is a critical part of the data that are reflected,” he said. “Equally important is that such stories and similar activities are intentionally processed to enable students to make the connections between personal experience and relevant theory.”

He also urged them to challenge the ways in which knowledge had been framed through oppression.

“Schools are often characterised by messages that draw on one or another form of oppression. Thus, expectations are subtly or in some cases unsubtly communicated, e.g. that girls are not good at physics, or that, while white learners are strong in abstract thought, African learners have untapped creativity, and so on,” he continued.

“For someone to integrate into their role as educators a commitment against oppression means confronting obstacles that one may previously have shied away from, such as challenging authority, naming privilege, emphasising the power relations that exist between social groups, listening to people one has previously ignored, and risking being seen as deviant, troublesome or unpopular.”

Furthermore, Prof. Francis said dealing with diversity in education was always affectively loaded for both students and teachers. He said in South Africa one injunction from educators was to be “sensitive” and thus avoid risking engagement with the contentious issues around imbalances of power.

“If both students and teachers are to confront issues of oppression and power in any meaningful way, we need to design more purposely for the difficulties they will encounter, for example, creating a classroom environment that promotes safety and trust so that all students are able to confront and deal with prejudice and discrimination. Classroom environments will need to balance the affective and cognitive in addressing issues of diversity and social justice,” he added.

He also said that teachers should recognise the need to complement changing attitudes with attempts to change the structural aspects of oppressions.

“To prevent superficial commitments to change, it is important for students to explore barriers that prevent them from confronting oppressive attitudes and behaviours. In this way students are able to learn and see the structural aspects of oppression,” he said.

“Equally important, however, is to get students to examine the benefits associated with challenging oppression. A fair amount of time must therefore be spent on developing strategies with students which they will be able to use practically in challenging oppression.”

He also advised educators to affirm the capacity of staff and learners to act and learn in ways that do not replicate patterns of oppression.

“Many South African schools have survived both the harsh repression of apartheid and the continuing legacy of oppression of various kinds. Despite that, we are often as educators made aware of the ways in which young people in particular affirm themselves and each other in creative and confident ways,” he concluded.

Media Release
Issued by: Lacea Loader
Director: Strategic Communication (acg)
Tel: 051 401 2584
Cell: 083 645 2454
E-mail: loaderl@ufs.ac.za  
7 October 2010
 

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