Leveraging Zebrafish and Electrochemistry to Search for Therapies to Delay Cognitive Decline

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Presenter(s)

Hannah Chern

Abstract or Description

Cognitive decline, a medical condition commonly associated with dementia, affects about 1 in 9 adults worldwide, and there is a growing interest in therapeutic interventions centered around reducing and preventing it. One expedient way to study cognitive decline is to leverage animal models, which can display symptom onset in months. Furthermore, we employ fast-scan cyclic voltammetry (FSCV) on their brains, which allows for efficient measurement of neuronal signaling of compounds like dopamine (DA). DA, an abundant neurotransmitter that plays critical roles in cognitive and motor functions, is an excellent chemical target to probe in zebrafish brains to assess cognitive function since disturbances in DA synthesis, storage, and release are involved in the occurrence of cognitive decline. Here, we will show how DA release is modified in a cognitively declined model organism, zebrafish, and test the possibility of preventing the decline in DA signaling with carnosine, a small molecule that has been previously proposed to have neuroprotective effects.

Zebrafish were dosed with okadaic acid, a neurotoxin known to induce hyperphosphorylation in zebrafish brain along with behavioral changes associated with Alzheimer’s disease. Using FSCV at carbon-fiber microelectrodes, we conducted a neurochemical analysis to assess changes in stimulated DA release in zebrafish whole brains. We observed a significant impairment in DA release within the zebrafish dementia model. Next, we investigated whether this impairment may be rescued by long-term administration of carnosine. Carnosine significantly enhances DA release in the zebrafish brain when compared with the dementia model. These studies, in concert with latent learning studies on these fish, which are also ongoing in our lab, provide strong support that carnosine should be further explored for its neuroprotective effects; additionally, this workflow provides a convenient platform for studying potential cognitive interventions.

Mentor

Romana Jarosova