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

Autor: Wei Sun, Zhenzhong Lu, Xiao Chen, null Yang, Yazi Mei, Xiaoliang Li, Lei An
Rok vydání: 2022
Předmět:
Zdroj: ACS Chemical Neuroscience. 13:3352-3361
ISSN: 1948-7193
DOI: 10.1021/acschemneuro.2c00383
Popis: Studies demonstrated that alumina nanoparticles (alumina NPs) impair spatial cognition and hippocampus-dependent synaptic plasticity. Although alumina NPs accumulate in the prefrontal cortex (PFC), their effects on PFC-mediated neuronal and cognitive function have been not yet documented. Here, alumina NPs (10 or 20 μg/kg of body weight) were bilaterally injected into the medial PFC (mPFC) of adult rats, and the levels of glycogen synthase kinase 3β (GSK3β) and the brain-derived neurotrophic factor (BDNF) were detected. The PFC-dependent working memory task with one-minute or three-minute delay time was conducted. Meanwhile, the neuronal correlates of working memory performance were recorded. The specific expression of neuronal BDNF was assessed by colabeled BDNF expression with the neuronal nuclear antigen (NeuN). Whole-cell patch-clamp recordings were employed to detect neuronal excitability. Intra-mPFC alumina NP infusions significantly enhanced the expression of GSK3β but reduced the phosphorylation of GSK3β (pGSK3β) and BDNF levels more severely at a dose of 20 μg/kg. Alumina NPs acted in a dose-dependent manner to impair working memory. The neuronal expression of BDNF in the 20 μg/kg group was markedly declined compared with the 10 μg/kg group. During the delay time, the neuronal frequency of pyramidal cells but not interneurons was significantly weakened. Furthermore, both the frequency and amplitude of the excitatory postsynaptic currents (EPSCs) were descended in the mPFC slices. Additionally, the infusion of GSK3β inhibitor SB216763 or BDNF could effectively attenuate the impairments in neuronal correlate, neuronal activity, and working memory. From the perspective of the identified GSK3β/BDNF pathway, these findings demonstrated for the first time that alumina NPs exposure can be a risk factor for prefrontal neuronal and cognitive functions.
Databáze: OpenAIRE