Suppression of neurite outgrowth of primary cultured hippocampal neurons is involved in impairment of glutamate metabolism and NMDA receptor function caused by nanoparticulate TiO2

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

“…NPs could decrease glutamine synthetase (GS) activity, increase phosphateactivated glutaminase (PAG) activity, and reduce the production of ATP by causing [60] NPs such as Ag NPs have been shown to affect excitatory glutamatergic synaptic transmission and receptor function [43]. An in vitro study indicated that inorganic NPs could reduce the expression of NR1 and NR2 [25], weakening the ability of the NMDAR to interact with glutamate and glycine. Moreover, it has been suggested that in vivo, the upregulation of genes related to DA could be the mechanism causing the effects of inorganic NPs [96].…”

“…An in vitro study found that TiO 2 NPs could significantly increase the cytoplasmic Ca -ATPase in primary cultured hippocampal neurons [25]. Other NPs, e.g., CdSe quantum dots [73] and ZnO NPs [74], have also been reported to increase intracellular Ca 2+ levels rapidly and persistently in cells via Ca 2+ influx from the extracellular spaces and/or intracellular calcium stores, while gold NPs did not induce this intracellular calcium response [43].…”

“…Treatment with TiO 2 NPs increased the Glu content and altered the Glu metabolism in primary hippocampal neurons [25]. Ag NPs have been shown to have no effect on presynaptic glutamate release, but they could change the postsynaptic receptor sensitivity to glutamate by reducing the amplitude of miniature excitatory post synaptic currents, leading to increased levels of glutamate in the brain [91].…”

“…NPs can clearly increase the levels of ROS in the brain, according to in vivo [15,42] and in vitro [25,29,43,44] studies, and this could be one of the main toxic effects of inorganic NPs on cell physiology. ROS comprise several reactive molecules containing oxygen constituents, including superoxide anions (O 2 -), hydroxyl ions (OH -), peroxynitrite anions (ONOO -) and hydrogen peroxide (H 2 O 2 ).…”

“…I K and I A current-voltage curve were reported to be influenced after treatment with TiO 2 NPs [25 ], and ZnO NPs [69], CuO NPs [76], and tungsten carbide NPs [77]. Ag NPs have been found to affect the VGKCs by producing a hyperpolarizing shift in the inactivation-voltage curve of I A and the activation-voltage curve of I K as well as by postponing the recovery of I A from the inactivation state, thereby altering mouse primary CA1 neuron excitability [78].…”