Zebrafish Model of Cognitive Dysfunction

Cognitive dysfunction is an impairment in one or more of the six cognitive domains (complex attention, executive function, learning and memory, language, perceptual motor and social cognition). The effect of pharmacological interventions can be studied using animal models of cognitive dysfunction, which are typically split into pharmacological, developmental and genetic models. Rodents are the most commonly used animal species for modelling cognitive dysfunction, although multiple models and test locations are often recommended to improve validity. Researchers thus unfortunately need to balance the validity of their experimental designs with financial, logistical and cost constraints. Zebrafish could be the answer to this conundrum as one of their many advantages over rodents is their high breeding rate which makes high-throughput screening more feasible and thus increases cost-effectiveness. The popularity of zebrafish has been increasing in recent times, as measured by the increasing number of zebrafish research publications. It is thus unsurprising that several zebrafish models of cognitive dysfunction have already been developed, together with zebrafish tests designed to measure zebrafish cognitive performance. Future research will undoubtedly lead to the development of new zebrafish models of cognitive dysfunction, as well as validate current ones to pave the way for widespread adoption

Channa striatus in inflammatory conditions: A systematic review

Channa striatus (CS), or snakehead murrel, is an obligate air-breathing freshwater fish. Besides its wound healing properties, CS has also been reported to exhibit anti-inflammatory effects in multiple studies. While there are anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), their long-term use is associated with an increased risk of peptic ulcers, acute renal failure, stroke, and myocardial infarction. Thus, it is essential to look at natural methods such as CS extract. While there is an abundant number of investigative studies on the inflammatory properties of CS, the quality of these studies has not been evaluated effectively. Thus, this review aims to summarise, evaluate, and critically appraise currently available literature regarding the anti-inflammatory properties of CS extract. This is done by performing a search using four databases, namely Google Scholar, Embase via Elsevier, Scopus, and Web of Science, with the following terms: Channa striatus AND inflammation. From our review, CS has been experimentally shown to positively affect inflammatory conditions such as gastric ulcers, dermatitis, osteoarthritis, and allergic rhinitis. Beneficial effects were also found on inflammation in the presence of tuberculosis and in situations that involve inflammation, such as wound healing. While CS clearly has potential for treating inflammatory conditions, much work needs to be done on identifying and isolating the active constituents before exact mechanisms of action can be worked out to develop future anti-inflammatory medications

Identification of curcumin analogues with anti-seizure potential in vivo using chemical and genetic zebrafish larva seizure models

Seizures are the outward manifestation of abnormally excessive or synchronous brain activity. While seizures can be somewhat symptomatically managed with anti-epileptic drugs (AEDs), many patients are still refractory to the currently available AEDs. As a result, there is a need to identify new molecules with anti-seizure properties. Curcumin is the principle curcuminoid of Curcuma longa, or colloquially turmeric, and has been experimentally proven to have anti-convulsive properties, but its poor bioavailability has dampened further therapeutic interest. Hence, this study aimed to ask if structural analogues of curcumin with an adequate bioavailability could have an anti-seizure effect in vivo. To do so, we tested these analogues following a multipronged approach combining the use of several zebrafish seizure models (chemically-induced and genetic) and complementary assays (behavioural and brain activity). Overall, from the 68 analogues tested, we found 15 different derivatives that were able to significantly decrease the behavioural hyperactivity induced by pentylenetetrazol. Of those, only a few showed an effect on the hyperactivity phenotype of two genetic models of brain seizures that are the gabra1 and gabrg2 knockouts. Two analogues, CA 80(1) and CA 74(1), were able to significantly alleviate brain seizures of gabrg2-mutant larvae. As a result, these analogues are good candidates as novel anti-seizure agents

Orthosiphon stamineus Leaf Extract Affects TNF-α and Seizures in a Zebrafish Model

Epileptic seizures result from abnormal brain activity and can affect motor, autonomic and sensory function; as well as, memory, cognition, behavior, or emotional state. Effective anti-epileptic drugs (AEDs) are available but have tolerability issues due to their side effects. The Malaysian herb Orthosiphon stamineus, is a traditional epilepsy remedy and possesses anti-inflammatory, anti-oxidant and free-radical scavenging abilities, all of which are known to protect against seizures. This experiment thus aimed to explore if an ethanolic leaf extract of O. stamineus has the potential to be a novel symptomatic treatment for epileptic seizures in a zebrafish model; and the effects of the extract on the expression levels of several genes in the zebrafish brain which are associated with seizures. The results of this study indicate that O. stamineus has the potential to be a novel symptomatic treatment for epileptic seizures as it is pharmacologically active against seizures in a zebrafish model. The anti-convulsive effect of this extract is also comparable to that of diazepam at higher doses and can surpass diazepam in certain cases. Treatment with the extract also counteracts the upregulation of NF-κB, NPY and TNF-α as a result of a Pentylenetetrazol (PTZ) treated seizure. The anti-convulsive action for this extract could be at least partially due to its downregulation of TNF-α. Future work could include the discovery of the active anti-convulsive compound, as well as determine if the extract does not cause cognitive impairment in zebrafish

Orthosiphon stamineus proteins alleviate pentylenetetrazol-induced seizures in Zebrafish

The anticonvulsive potential of proteins extracted from Orthosiphon stamineus leaves (OSLP) has never been elucidated in zebrafish (Danio rerio). This study thus aims to elucidate the anticonvulsive potential of OSLP in pentylenetetrazol (PTZ)-induced seizure model. Physical changes (seizure score and seizure onset time, behavior, locomotor) and neurotransmitter analysis were elucidated to assess the pharmacological activity. The protective mechanism of OSLP on brain was also studied using mass spectrometry-based label-free proteomic quantification (LFQ) and bioinformatics. OSLP was found to be safe up to 800 µg/kg and pre-treatment with OSLP (800 µg/kg, i.p., 30 min) decreased the frequency of convulsive activities (lower seizure score and prolonged seizure onset time), improved locomotor behaviors (reduced erratic swimming movements and bottom-dwelling habit), and lowered the excitatory neurotransmitter (glutamate). Pre-treatment with OSLP increased protein Complexin 2 (Cplx 2) expression in the zebrafish brain. Cplx2 is an important regulator in the trans-SNARE complex which is required during the vesicle priming phase in the calcium-dependent synaptic vesicle exocytosis. Findings in this study collectively suggests that OSLP could be regulating the release of neurotransmitters via calcium-dependent synaptic vesicle exocytosis mediated by the “Synaptic Vesicle Cycle” pathway. OSLP’s anticonvulsive actions could be acting differently from diazepam (DZP) and with that, it might not produce the similar cognitive insults such as DZP