Global Proteomic Profile of Aluminum-Induced Hippocampal Impairments in Rats: Are Low Doses of Aluminum Really Safe?

Abstract

Hippocampus is the brain area where aluminum (Al) accumulates in abundance and is widely associated with learning and memory. In the present study, we evaluate behavioral, tissue, and proteomic changes in the hippocampus of Wistar rats caused by exposure to doses that mimic human consumption of aluminum chloride (AlCl3) in urban areas. For this, male Wistar rats were divided into two groups: Control (distilled water) and AlCl3 (8.3 mg/kg/day), both groups were exposed orally for 60 days. After the Al exposure protocol, cognitive functions were assessed by the Water maze test, followed by a collection for analysis of the global proteomic profile of the hippocampus by mass spectrometry. Aside from proteomic analysis, we performed a histological analysis of the hippocampus, to the determination of cell body density by cresyl violet staining in Cornu Ammonis fields (CA) 1 and 3, and hilus regions. Our results indicated that exposure to low doses of aluminum chloride triggered a decreased cognitive performance in learning and memory, being associated with the deregulation of proteins expression, mainly those related to the regulation of the cytoskeleton, cellular metabolism, mitochondrial activity, redox regulation, nervous system regulation, and synaptic signaling, reduced cell body density in CA1, CA3, and hilus.

Antioxidant and protective activities of aqueous Theobroma cacao seed extract against aluminium-induced hippocampal toxicity in Wistar rats

“…The histological observations show atrophy and vacuolated astrocytes in the hippocampus of rats treated with aluminium only. This is in agreement with Bittencourt and colleagues in a report that aluminium causes hippocampal neurodegeneration and atrophy (Bittencourt et al, 2022). Hippocampal neurodegeneration and atrophy are reported to cause learning and memory deficits (Anand and Dhikav, 2012;Gemmell et al, 2012).…”

Intrahippocampal effects of Aluminum injection on affective and cognitive response in male Wistar rat: Potential role of oxidative stress

“…Histological analyses reveal that AlCl 3 mediates progressive alterations characterized by disorganization in the pyramidal cellular arrangement and a decrease in neuronal density in the CA3 hippocampal area as compared with the control group, which correlated with the biochemical changes revealed in this work. These ndings were correlated to those claimed by Bittencourt et al, ; Fernandes et al, and Maya et al, [24,32,41] These neurotoxic effects of Al may be justi ed by the tropism that this metal has for CNS structures and cause oxidative damage to hippocampal cells.…”

“…We selected the CA3 area for light microscopic analyses at magni cations of ×20. After, the photomicrographs were taken and analyzed using ImageJ software [23,24].…”

Shikonin Attenuate Behavioral Defects, Oxidative Stress, and Neuroinflammation During Aluminum Chloride-induced Alzheimer’s Disease Condition in an in vivo Experimental Model

“…We have used SHK in our study to treat the rats for experimentally induced AD using AlCl 3. As stated earlier, it is well known that AlCl 3 is a neurotoxicant to brain cells like neurons, astrocytes, glial cells, and vascular cells in both in vivo and in vitro experimental conditions (Bittencourt et al, 2022; Yang et al, 2019) and was also reported to be present in brain tissues of age-related dementia and Alzheimer’s patients (Exley & Clarkson, 2020).…”