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

Abstract

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.

Prenatal cyanuric acid exposure induced spatial learning impairments associated with alteration of acetylcholine-mediated neural information flow at the hippocampal CA3-CA1 synapses of male rats

“…As described previously, [59][60][61] microelectrodes were arranged in two four by four matrix using 25-μm-diameter platinum/iridium wire, coated with polyimide (California Fine Wire Company) in a 16-gauge silica tube (World Precision Instruments). It was then attached via gold pins to an EIB-36-PTB board (Neuralynx Inc.), which was assembled to a microdrive (Harlan 8-drive; Neuralynx).…”

Neuromodulatory Effect of BDNF in Spinal Cord Injury

“…Second, BDNF modulates synaptic transmission by regulating the release of neurotransmitters and the expression of neurotransmitter receptors. The protein achieves this effect by activating downstream signaling pathways that regulate the expression and trafficking of neurotransmitter receptors [13].…”

“…Third, BDNF promotes the generation and propagation of action potentials by regulating the expression and activity of voltage-gated ion channels [13].…”