Intracellular Gold Nanoparticles Increase Neuronal Excitability and Aggravate Seizure Activity in the Mouse Brain

Abstract

Due to their inert property, gold nanoparticles (AuNPs) have drawn considerable attention; their biological application has recently expanded to include nanomedicine and neuroscience. However, the effect of AuNPs on the bioelectrical properties of a single neuron remains unknown. Here we present the effect of AuNPs on a single neuron under physiological and pathological conditions in vitro. AuNPs were intracellularly applied to hippocampal CA1 neurons from the mouse brain. The electrophysiological property of CA1 neurons treated with 5- or 40-nm AuNPs was assessed using the whole-cell patch-clamp technique. Intracellular application of AuNPs increased both the number of action potentials (APs) and input resistance. The threshold and duration of APs and the after hyperpolarization (AHP) were decreased by the intracellular AuNPs. In addition, intracellular AuNPs elicited paroxysmal depolarizing shift-like firing patterns during sustained repetitive firings (SRF) induced by prolonged depolarization (10 sec). Furthermore, low Mg2+-induced epileptiform activity was aggravated by the intracellular AuNPs. In this study, we demonstrated that intracellular AuNPs alter the intrinsic properties of neurons toward increasing their excitability, and may have deleterious effects on neurons under pathological conditions, such as seizure. These results provide some considerable direction on application of AuNPs into central nervous system (CNS)

Gold Nanorod-assisted Optical Stimulation of Neuronal Cells

“…A moderate stimulation caused by the NPs without any laser irradiation (poly(styrenesulfonate)-coated and silica-coated only) was detected in the percentage of neurons with neurites 12 . These results are in line with recently published observations that gold nanoparticles can increase neuronal activity in vitro 23,24 . Figure 2 shows an example of epifluorescence images of differentiated NG108-15 neuronal cells cultured alone (Figure 2A) or with Au NRs (Figure 2B) and irradiated with different laser powers (indicated in the figure).…”

Potential Links between Cytoskeletal Disturbances and Electroneurophysiological Dysfunctions Induced in the Central Nervous System by Inorganic Nanoparticles

“…Although gold NPs were found to not significantly affect I Na [87], other inorganic NPs, e.g., Ag NPs have been found to affect the VGSCs by decreasing the amplitude of the I Na current, and thus altering mouse primary CA1 neuron excitability [88]. Furthermore, treatment with CdSe quantum dots could enhance I Na activation and inactivation by extending the I Na activation process and delaying I Na recovery, leading to a reduced fraction of available VGSCs…”

Patent Highlights April–May 2015

“…Whole-cell voltage-clamp recordings confirmed that synaptic NMDA receptors remained essentially unaffected. Caution is advisable here because gold nanoparticles of that size, though chemically inert, have been reported to increase neuronal excitability [37]. Despite innovations such as the proteasome inhibitor, bortezomib (Millennium/Takeda's and Janssen's Velcade ® ) and lenalidomide (Celgene's Revlimid ® ), multiple myeloma remains one of the most serious challenges in cancer therapy.…”