Aluminum Chloride-Induced Planarian Model with Cognitive Impairments Through Neuronal Damage, Neurotransmitter Imbalance, Apoptosis, and Oxidative Stress

The prevalence of Alzheimer’s disease has significantly increased, which will place a heavy burden on families and society. Cognitive impairment is a typical feature of Alzheimer’s disease. Rodent models play a key role in AD research, but their considerable expense and slow development pose challenges to the pace of therapeutic discovery. Here, we established a new model of cognitive dysfunction in planarians using AlCl3. After exposure to 50 μM AlCl3 for 48 h, the planarians exhibited cognitive dysfunction in the phototaxis test, dual-stimulus decision test and T-maze test. Immunohistochemical and immunofluorescence experiments confirmed that AlCl3 damaged the neural structure of planarians. Moreover, AlCl3 disrupted the balance of neurotransmitters, leading to cell apoptosis and oxidative stress. Finally, we confirmed that donepezil alleviated the cognitive impairment caused by AlCl3. This indicates that the model we established for cognitive dysfunction in planarians was feasible. However, planarians lack the amyloid-β plaques and tau neurofibrillary tangles typical of AD. Therefore, the planarian model can be considered a promising complementary platform for high-throughput screening of candidate drugs for cognitive impairment.