Aluminium oxide nanoparticles compromise spatial memory performance and proBDNF-mediated neuronal function in the hippocampus of rats

Abstract

Background Alumina nanoparticles (aluminaNPs), which are widely used in a range of daily and medical fields, have been shown to penetrate blood-brain barrier, and distribute and accumulate in different brain areas. Although oral treatment of aluminaNPs induces hippocampus-dependent learning and memory impairments, characteristic effects and exact mechanisms have not been fully elucidated. Here, male adult rats received a single bilateral infusion of aluminaNPs (10 or 20 µg/kg of body weight) into the hippocampal region, and their behavioral performance and neural function were assessed. Results The results indicated that the intra-hippocampus infusions at both doses of aluminaNPs did not cause spatial learning inability but memory deficit in the water maze task. This impairment was attributed to the effects of aluminaNP on memory consolidation phase through activation of proBDNF/RhoA pathway. Inhibition of the increased proBDNF by hippocampal infusions of p75NTR antagonist could effectively rescue the memory impairment. Incubation of aluminaNPs exaggerated GluN2B-dependent LTD induction with no effects on LTD expression in hippocampal slices. AluminaNP could also depress the amplitude of NMDA-GluN2B EPSCs. Meanwhile, increased reactive oxygen specie production was reduced by blocking proBDNF-p75NTR pathway in the hippocampal homogenates. Furthermore, the neuronal correlate of memory behavior was drastically weakened in the aluminaNP-infused groups. The dysfunction of synaptic and neuronal could be obviously mitigated by blocking proBDNF receptor p75NTR, implying the involvement of proBDNF signaling in aluminaNP-impaired memory process. Conclusions Taken together, our findings provide the first evidence that the accumulation of aluminaNPs in the hippocampus exaggeratedly activates proBDNF signaling, which leads to neural and memory impairments.

Aluminum Oxide Nanoparticles Impair Working Memory and Neuronal Activity through the GSK3β/BDNF Signaling Pathway of Prefrontal Cortex in Rats

“…79 All the tests were initiated 15 min following saline or aluminaNP infusions because 15 min after aluminaNP infusions, the changes of the neural synchrony could be detected in both the antennal lobe 53 and hippocampus. 10 To detect the involvement of GSK3β-BDNF signaling in the aluminaNP-induced working memory impairment, rats were bilateral infused GSK3β inhibitor SB216763 (5.0 μM, cat#S3442, Sigma-Aldrich) or recombinant human BDNF (1.5 μg/ μL, cat#248-BD, R&D Systems) into the mPFC 15 min prior to the alumina treatment. The doses of aluminaNP were relatively low compared with other investigations, 76,77,79−81 and other drug preparation and administration were according to previous studies.…”

“…Also, the atomic percentages of aluminum and oxygen were 39.03 and 60.81% correspondingly. Furthermore, silver staining was employed to detect the location of nanoparticles as described previously. , Following the previous methods, − aluminaNPs were dissolved in 0.9% saline solution to a concentration of 10.0 or 20.0 μg/μL and bilaterally injected with a dose of 10 or 20 μg/kg of body weight into the mPFC area. The suspension was freshly prepared for each experiment and sonicated at 28 °C before each infusion to reach a homogeneous dispersion, as previously described …”

“…Aluminum oxide nanoparticles (aluminaNPs) have attracted wide interest among the most important nanometals because of their promising technological applications, including industry, agriculture, medicine, food, and others. , Studies have shown that alumina NPs can enter the brain through the blood–brain barrier (BBB) despite the route of administration because of the small size and their effects on the BBB permeability, , resulting in localizing in various organs and brain regions such as the hippocampus, striatum, olfactory bulb, and prefrontal cortex (PFC). , Previous findings have documented that chronic exposure to aluminaNPs could result in neurotoxicity in the form of increased brain aluminum content, disturb brain energy homeostasis, and impair the hippocampus-dependent memory. , Meanwhile, aluminaNPs enhanced the amyloid beta (Aβ) production and aggregation in the hippocampus of these animals. Maternal aluminaNP exposure could stunt neurodevelopmental behaviors and increase anxiety-like behavior owing to alterations in neurotransmitter enzyme levels in the brain .…”

“…8,9 Previous findings have documented that chronic exposure to aluminaNPs could result in neurotoxicity in the form of increased brain aluminum content, disturb brain energy homeostasis, and impair the hippocampus-dependent memory. 7,10 Meanwhile, aluminaNPs enhanced the amyloid beta (Aβ) production and aggregation in the hippocampus of these animals. Maternal aluminaNP exposure could stunt neurodevelopmental behaviors and increase anxiety-like behavior owing to alterations in neurotransmitter enzyme levels in the brain.…”

Ultrasensitive Functionalized Polymeric-Nanometal Oxide Sensors for Potentiometric Determination of Ranitidine Hydrochloride

“…Aluminum oxide nanoparticles (Al 2 O 3 NPs) is a type of metal oxide nanoparticle used in various biomedical purposes due to their unique physicochemical and structural properties, including resistance to wear, chemicals, and mechanical stresses, as well as good optical properties and a porous large surface area. Another reason for Al 2 O 3 NPs extensive use is their inexpensive preparation cost and ease of handling [ 8 , 9 ].…”