AlCl₃ induced learning and memory deficit in zebrafish

Aluminium is a metal known to cause neurotoxicity in the brain, by promoting neurodegeneration and affecting memory and cognitive ability. AlCl₃ has been reported to enhance reactive oxygen species (ROS) and inflammatory markers which are further responsible for the degeneration of neurons. AlCl₃ exposure to zebrafish causes behavioral, biochemical, and neurochemical changes in the brain. In our study, Zebrafish were exposed to AlCl₃ at three different doses (50 µg/L, 100 µg/L, and 200 µg/L) for four consecutive days. On days 1st and 4th, a novel diving test was performed to check anxiety in zebrafish. T - maze and novel object recognition test were used to check the memory on days 3rd and 4th with the help of ANY-maze software. On the last day (4th day), zebrafishes were sacrificed and whole brains were used to perform the biochemical, neurotransmitters, histopathological, and immunohistochemistry analysis. Our study revealed that AlCl₃ exposure significantly decreased the total distance traveled, and the number of entries in the top zone and increased the time spent in the bottom zone, checked through the novel diving test. In the T maze test, AlCl₃ treated zebrafish showed significantly increased transfer latency to the favorable zone and time spent, and the number of entries to the unfavorable zone. The exploration time with the novel object was reduced significantly after AlCl₃ treatment. Moreover, reduced glutathione (GSH) and superoxide dismutase (SOD) levels were significantly reduced in AlCl₃ treated zebrafish whereas malondialdehyde (MDA) level was found to be increased, indicating high oxidative stress. The neurotransmitters level was also disturbed indicated by the significantly decreased GABA, dopamine, noradrenaline, and Serotonin levels and increased glutamate level in the brain of zebrafish treated with AlCl₃. Moreover, histopathological and immunohistochemistry study shows a markedly increased number of pyknotic neurons and reduced the expression of Nrf2 in the zebrafish brain after AlCl₃ exposure. These findings suggest that AlCl₃ significantly causes behavioral, biochemical, neurotransmitters, morphological, and molecular changes in zebrafish, ultimately causing AD.