Influences of nanoparticle zinc oxide on acutely isolated rat hippocampal CA3 pyramidal neurons.

The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, China.
NeuroToxicology (Impact Factor: 2.65). 12/2008; 30(2):220-30. DOI: 10.1016/j.neuro.2008.12.005
Source: PubMed

ABSTRACT The effects of zinc oxide nanoparticles (nano-ZnO) on the properties of voltage-dependent sodium, potassium currents and evoked action potentials were studied in acutely isolated rat hippocampal CA3 pyramidal neurons at postnatal ages of 10-14 days rats using the whole-cell patch-clamp technique. The results indicated that: (1) in the present of final concentration of 10(-4)g/ml nano-ZnO, the current-voltage curve of sodium current (I(Na)) was decreased, and the peak amplitudes of I(Na) were increased considerably from -50 to +20mV (p<0.05). Meanwhile, the inactivation and the recovery from inactivation of I(Na) were also promoted by the nano-ZnO solution (10(-4)g/ml) (p<0.01). However, the steady-state activation curve of I(Na) was not shifted by the nano-ZnO. (2) The amplitudes of transient outward potassium current (I(A)) were increased by the nano-ZnO solution (10(-4)g/ml), while the current-voltage curve of delayed rectifier potassium current (I(K)) was significantly increased from +20 to +90mV (p<0.05). However, it is apparent that the nano-ZnO solution did not shift the steady-state activation curve of I(A) and I(K), and neither had significant effects on the inactivation and the recovery from inactivation of I(A). (3) Peak amplitude and overshoot of the evoked single action potential were increased and half-width was diminished in the presence of the 10(-4)g/ml nano-ZnO solution (p<0.05). Simultaneously, a prolonged depolarizing current injection enhanced (p<0.05) repetitive firing evoked firing rate. These results suggested that 10(-4)g/ml nano-ZnO solution can lead to an enhancement in the current amplitudes of I(Na) and I(K) by increasing the opening number of sodium channels, delaying rectifier potassium channels, and enhancing the excitability of neurons, which lead to Na(+) influx and the accumulation of intracellular Na(+), as well as K(+) efflux plus the loss of cytoplasmic K(+). These may disturb the ionic homeostasis and the physiological functions of neurons.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the last 30 years, the use of engineered nanoparticles (NPs) has progressively increased in many industrial and medical applications. In therapy, NPs may allow more effective cellular and subcellular targeting of drugs. In diagnostic applications, quantum dots are exploited for their optical characteristics, while superparamagnetic iron oxides NPs are used in magnetic resonance imaging. NPs are used in semiconductors, packaging, textiles, solar cells, batteries and plastic materials. Despite the great progress in nanotechnologies, comparatively little is known to date on the effects that exposure to NPs may have on the human body, in general and specifically on the brain. NPs can enter the human body through skin, digestive tract, airways and blood and they may cross the blood-brain barrier to reach the central nervous system. In addition to the paucity of studies describing NP effects on brain function, some of them also suffer of insufficient NPs characterization, inadequate standardization of conditions and lack of contaminant evaluation, so that results from different studies can hardly be compared. It has been shown in vitro and in vivo in rodents that NPs can impair dopaminergic and serotoninergic systems. Changes of neuronal morphology and neuronal death were reported in mice treated with NPs. NPs can also affect the respiratory chain of mitochondria and Bax protein levels, thereby causing apoptosis. Changes in expression of genes involved in redox pathways in mouse brain regions were described. NPs can induce autophagy, and accumulate in lysosomes impairing their degradation capacity. Cytoskeleton and vesicle trafficking may also be affected. NPs treated animals showed neuroinflammation with microglia activation, which could induce neurodegeneration. Considering the available data, it is important to design adequate models and experimental systems to evaluate in a reliable and controlled fashion the effects of NPs on the brain, and generate data representative of effects on the human brain, thereby useful for developing robust and valid nanosafety standards.
    Progress in Neurobiology 05/2014; · 9.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It has been documented in in vitro studies that zinc oxide nanoparticles (ZnO NPs) are capable of inducing oxidative stress, which plays a crucial role in ZnO NP-mediated apoptosis. However, the underlying molecular mechanism of apoptosis in neurocytes induced by ZnO NP exposure was not fully elucidated. In this study, we investigated the potential mechanisms of apoptosis provoked by ZnO NPs in cultured primary astrocytes by exploring the molecular signaling pathways triggered after ZnO NP exposure. ZnO NP exposure was found to reduce cell viability in MTT assays, increase lactate dehydrogenase (LDH) release, stimulate intracellular reactive oxygen species (ROS) generation, and elicit caspase-3 activation in a dose- and time-dependent manner. Apoptosis occurred after ZnO NP exposure as evidenced by nuclear condensation and poly(ADP-ribose) polymerase-1 (PARP) cleavage. A decrease in mitochondrial membrane potential (MMP) with a concomitant increase in the expression of Bax/Bcl-2 ratio suggested that the mitochondria also mediated the pathway involved in ZnO NP-induced apoptosis. In addition, exposure of the cultured cells to ZnO NPs led to phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-related kinase (ERK), and p38 mitogen-activated protein kinase (p38 MAPK). Moreover, JNK inhibitor (SP600125) significantly reduced ZnO NP-induced cleaved PARP and cleaved caspase-3 expression, but not ERK inhibitor (U0126) or p38 MAPK inhibitor (SB203580), indicating that JNK signaling pathway is involved in ZnO NP-induced apoptosis in primary astrocytes.
    Nanoscale Research Letters 03/2014; 9(1):117. · 2.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nanotechnology is having a tremendous impact on our society. However, societal concerns about human safety under nanoparticle exposure may derail the broad application of this promising technology. Nanoparticles may enter the human body via various routes, including respiratory pathways, the digestive tract, skin contact, intravenous injection, and implantation. After absorption, nanoparticles are carried to distal organs by the bloodstream and the lymphatic system. During this process, they interact with biological molecules and perturb physiological systems. Although some ingested or absorbed nanoparticles are eliminated, others remain in the body for a long time. The human body is composed of multiple systems that work together to maintain physiological homeostasis. The unexpected invasion of these systems by nanoparticles disturbs normal cell signaling, impairs cell and organ functions, and may even cause pathological disorders. This review examines the comprehensive health risks of exposure to nanoparticles by discussing how nanoparticles perturb various physiological systems as revealed by animal studies. The potential toxicity of nanoparticles to each physiological system and the implications of disrupting the balance among systems are emphasized.
    Chemical Society Reviews 03/2014; · 24.89 Impact Factor

Full-text (2 Sources)

Available from
Jun 14, 2014