Nootropic, Neuroprotective and Anti-oxidant Role of Apocynin in Scopolamine Induced Memory Deficit in a Zebrafish Model

Four decades of search in quest of an effective therapeutic option for Alzheimer’s disease (AD) has led to a complete clinical failure, putting pre-clinical models, their evaluation in spotlight. The pre-clinical stage if lead with a systemic approach, than jumping straight into clinical trials, will reduce financial burden opening avenues for effective AD therapeutics. Preliminary screening therefore shall be fast, ensuring use of efficient, easy, and less time consuming pre-clinical models for screening new entities. Aim of present research was therefore development of a quick, effective, and easy zebrafish model for preliminary screening of probable AD therapeutics. The present research used total of 72 zebrafish divided into six groups, control, negative control, vehicle control, and 3 groups for apocynin (10 mg/kg, 30 mg/kg, and 70 mg/kg). We investigated memory retention, long term memory retention using passive avoidance paradigm, free radical generation using DCFDA assay, and glial cell proliferation using H and E histological staining. Intraperitoneally administered scopolamine (0.025 mg/kg) induced memory deficits hindering memory formation. Apocynin at all doses prevented scopolamine-induced amnesia. Apocynin was found to be capable of reducing free radical load and curbing the inflammation due to scopolamine administration. Moreover; long term memory retention was observed with 10 mg/kg apocynin. Our revelations designate the fact that passive avoidance model in zebrafish could be used as an acute model in order to screen potential entities for treatment of AD. Our findings highlight that a single dose of apocynin could reverse memory deficits induced by single scopolamine injection by acting on cholinergic transmission pathway. Apocynin being an anti-oxidant reduced the free radical generation, thus engaging one of the crucial pathways toward AD pathophysiology. In addition it offered neuroprotection by reducing glial cell proliferation. In conclusion apocynin exhibited multifaceted pharmacological activities like being nootropic, neuroprotective, and anti-oxidant in preclinical AD model. of the neuronal environment. Administration of single dose of SCP demonstrates the highest score for glial cell proliferation and hence the severe neuronal damage. The damage was totally reversed by apocynin 10 mg/kg and 30 mg/kg as evident with nil glial cell proliferation. The other dose of apocynin 70 mg/kg was effective compared to the negative control group, but could not completely reverse the damage. Apocynin thus bestowed neuroprotection by mitigating the neuronal damage, ultimately maintaining the neuronal homeostasis against the mulct of scopolamine administration. Our study reveals and advocates that passive avoidance test in zebrafish can be used as an acute preliminary in-vivo model to screen potential anti-Alzheimer entities. Our findings emphasize that the phytoactive apocynin reversed the memory deficits and retained the memory hampered by scopolamine administration. Apocynin thus is a nootropic with the probable mechanism being through the action on cholinergic transmission pathway. Apocynin being an anti-oxidant reduced the free radical generation, thus engaging one of the crucial pathways toward AD pathophysiology. Additionally it conferred neuroprotection by reducing the glial cell proliferation. In summary apocynin exhibited multifaceted pharmacological activities like nootropic, anti-oxidant, and neuroprotective in preventing the devastatingly progressive nature of Alzheimer disease. The study also urges for exploring the potential of in further in-vivo animal models to warranty its use in clinical trials.